ECOLOGICAL BIOCHEMISTRY - Study Guide - V. M. Isaenko 2005

Chapter 6. ECOLOGICAL AND BIOCHEMICAL INTERACTIONS BETWEEN ANIMALS

6.3. Interactions between animals of different species

6.3.1. Allomone poisons as a chemical means of defense and predation

As previously noted, substances involved in potential interactions may function as allomones or kairomones.

The defensive action of poisonous substances produced by animals (esotoxins), as well as their role in predation, is realized through A wide variety of mechanisms: repellent (deterrent), nociceptive (pain-inducing), paralytic (immobilizing), and others.

All venomous and poisonous animals can be divided into two groups: primarily poisonous and secondarily poisonous (Fig. 6.9).

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Fig. 6.9. Classification of poisonous animals

Primarily poisonous animals include those that synthesize venom in specialized glands or contain toxic metabolic products. Based on the method of venom production and utilization, these animals are subdivided into actively poisonous and passively poisonous.

Actively poisonous animals that possess a specialized venom apparatus with a delivery device are referred to as armed. Typical Examples of such an apparatus—consisting of a venom gland with an excretory duct and an inoculation device—include the fangs of snakes, the stings of insects, and the spines and thorns of fish. The secretion of the venom glands is introduced into the victim's body parenterally, that is, outside the digestive tract.

Another group of actively poisonous animals consists of those whose venom apparatus lacks an inoculation device; these are unarmed actively poisonous animals. Examples include the dermal poison glands of amphibians, the anal glands of insects, and others. The toxic secretions of such glands produce a toxic effect upon contact with the victim's integument.

In passively poisonous animals (such as fish, Mollusks, and insects), the toxin is synthesized within the Organism and accumulated in various Organs and Tissues.

A large group of toxic animals comprises secondarily poisonous organisms, which accumulate exogenous toxins and exhibit toxicity only when ingested. Examples include fish and mollusks that accumulate cyanobacterial toxins in their bodies, or insects that feed on plants poisonous to other animals. As a rule, secondary toxicity does not ensure individual defense, but at the cost of the death of individual specimens, the survival chances of Selection/30.html">The population as a whole are increased.

The route by which toxins enter the victim's body is of great importance. Typically, protein-based venoms (from snakes, arachnids, etc.) are injected parenterally using an armed apparatus, as many of them are destroyed by the Enzymes of the gastrointestinal tract. At the same time, non-protein toxins are effective when ingested via the oral route (such as amphibian Alkaloids and the poisons of certain species of fish and mollusks). Some animals defend themselves by spraying their toxins in the form of an aerosol (e.g., bombardier beetles). The effectiveness of such toxins depends on the condition of the victim's integument and the local concentration of the toxic substance.

Once introduced into the body, a toxin is distributed unevenly, as its distribution is influenced by various barriers—capillary walls, Cell membranes, Blood-Brain and placental barriers, and others. From the site of inoculation, the toxins enter the BLOOD AND LYMPH. Most animal toxins undergo biotransformation within the organism, which to some extent determines the resistance of certain animals to specific venoms.

The Liver and Kidneys bear the primary burden of detoxification and excretion of toxins from the body. Consequently, these organs are typically damaged during poisoning. To some extent, toxic substances and their metabolites can also be excreted via other pathways, such as through the Skin or in breast milk.

Structure/149.html">The problem of animal resistance to their own venoms is of considerable significance. Several main mechanisms ensure the resistance of such organisms to toxins. The most effective is likely the localization of the toxin in specialized organs (glands), the walls of which prevent the toxin from spreading throughout the body. The gland Cells are insensitive to the action of the toxins and are thus resistant to them. Cytolytic Components of the venoms (mainly enzymes) remain inactive due to the presence of specific inhibitors. Upon entering the victim's body, the toxin is diluted by Body Fluids, the concentration of inhibitors decreases, and the enzyme

comprising the venom is activated. Glands that produce protein toxins typically contain proteinase inhibitors that protect them from proteolysis (found in snakes, scorpions, Coelenterates, and Hymenoptera).

Humoral defense against endogenous toxins also exists. For instance, the blood of certain snakes contains protein factors that inactivate the venom.

The absence or inaccessibility of receptors on The Plasma Membrane of cells in certain venomous animals (such as certain amphibians and rhizopods/fish) to their own venom components also protects these animals.

Allomone poisons of Protozoa. Highly potent toxins have been discovered in free-living protozoa belonging to the order Dinoflagellata (class Phytomastigina), the principal ones being saxitoxin, gonyaulatoxins, gymnodimine/gymmberotoxins, etc.

An ecological phenomenon known as "red tides" is associated with dinoflagellates. It is characterized by a red algal bloom of Water driven by the intensive reproduction of dinoflagellates. Within this zone, the mortality of A large number of fish and other organisms is observed.

It has been established that "red tides" contain different species of dinoflagellates depending on the region. For example, on the Atlantic coast of Canada and the Pacific coast of the USA, the most common species is Gonyaulax catenella; on the Atlantic coast of the USA, Gonyaulax tamarensis; on the Atlantic coast of Spain, Gonyaulax excavata and Noctiluca miliaris; in the English Channel, Gymnodinium vereficum; in Hong Kong, Pyrodinium bahamense; in the Gulf of Mexico, Gonyaulax monilata and Gymnodinium brevis, among others.

Saxitoxin, as already mentioned, is one of the toxins produced by dinoflagellates. Its molecule consists of a tetrahydropurine ring linked to two guanidine residues (Fig. 6.10).

Fig. 6.10. Structure of saxitoxin

In addition to saxitoxin, dinoflagellates such as Gonyaulax tamarensis, Gonyaulax excavata, and Gonyaluax cateneila produce gonyautoxins, which are structurally and functionally similar (Fig. 6.11).

Fig. 6.11. Structure of gonyautoxin

Note. In gonyautoxins II and III, the radical (R) is an α-OH or β-OH group, respectively.

The Toxic effects of saxitoxin and its analogs are associated with neurotropic activity and direct suppression of the respiratory center, leading to cardiovascular and respiratory dysfunctions. According to various estimates, the lethal dose for a 70 kg human is 0.3–1.0 mg. Death results from respiratory arrest.

There is species-specific sensitivity to saxitoxin: fish, mollusks, and amphibians are more resistant than warm-blooded animals. Mechanistically, this poison selectively blocks sodium channels in electrically excitable membranes.

Besides dinoflagellates, primary producers of saxitoxin and its analogs include the cyanobacterium Aphanizomenon flos-aquae and potentially others. Secondary poisonous animals that accumulate saxitoxin through food chains include mollusks (Saxidomus giganteus, Mytilus californianus, etc.) and coral reef crabs (Zosimus aeneus, Atergatas floridus, Platypodia granulus, among others).

Certain dinoflagellates, notably Gymnodinium brevis, produce gymberotoxins, which are also neurotoxins causing inflammation, convulsions, paralysis, and cardiovascular and respiratory disorders.

Dinoflagellates of the species Gymnodinium brevis produce lipophilic toxins that cause Muscle paralysis, hypersalivation, and cardiovascular and respiratory impairment. They also exhibit cytotoxic activity and are characterized by a high toxicity of 0.01 µg/kg.

Ciguatoxin and maitotoxin, which cause severe joint pain, impaired motor coordination, diarrhea, nausea, as well as cardiovascular and neurological disorders, are produced by the dinoflagellate Gambierdiscus toxicus.

ALLOMONE POISONS OF MARINE INVERTEBRATES. Invertebrates make up a significant portion of marine and oceanic fauna. Among them are numerous venomous species belonging to Sponges, cnidarians, worms, mollusks, and echinoderms.

Sponges. Sponges (Spongia) are typical passively poisonous animals. They contain a variety of substances with antibiotic, cytostatic, and toxic activities, including sesquiterpenoids, sterols, biogenic amines, and toxic Proteins.

A protein called suberitin has been isolated from the sponge Suberites domuncula. It exhibits neurotoxic activity, hemolyzes erythrocytes, and hydrolyzes ATP.

Extracts from the sponge Suberites inconstans exhibit cytotoxicity accompanied by cytoplasmic and karyoplasmic fragmentation, as well as the rupture of cellular and nuclear membranes. Bromophenols from Dysidea herbacea possess cytostatic activity. A number of sponge compounds, notably from Cryptotethya crypta, display antitumor effects. Overall, more than 50 furan, hydroquinone, and isonitrile sesquiterpenoids have been isolated from sponges.

Some of the toxic substances found in sponges are shown in Fig. 6.12.

Cnidarians. A characteristic feature of cnidarians (Coelenterata), which comprise up to 9,000 species (including jellyfish, sea anemones, and polyps), is the presence of stinging cells (nematocytes) that produce venoms used for defense against predators, as well as for paralyzing and killing prey. All cnidarians are carnivorous, feeding on a wide variety of organisms ranging from planktonic crustaceans to fish.

The venom of the stalked jellyfish Gonionemus vertens blocks N-cholinergic receptors in neuromuscular synapses and parasympathetic ganglia. Exposure to this venom causes the release of histamine and serotonin in the victim's body.

The venom of box jellyfish (order Cubomedusae), particularly Chironex fleckeri, is characterized by hemolytic and dermonecrotic properties and causes burning pain. It contains proteins, CARBOHYDRATES, and indole derivatives.

Envenomation by disk jellyfish (order Semeostomea), notably the lion's mane jellyfish Cyanea capillata, causes burning pain, erythema, and edema. The venom contains a mixture of toxic proteins. The venom of the sea nettle Chysaora quinquecirrha contains enzymes (DNases, RNases, ATPases, hyaluronidase, acid and alkaline Phosphatases, collagenase), various Peptides, amines, and Other Compounds. It exhibits cardiotoxic, hemolytic, and dermonecrotic activities and induces burning pain.

Fig. 6.12. Selected allomone poisons of sponges:

1 — sterol sulfates from the sponge Toxadocia zumi; 2 — latrunculins from the sponge Latruncula magnifica:

2a — latrunculin A, 2b — latrunculin B; 3 — axisonitrile-1 from the sponge Axinella cannabina; 4 — sesterpenes from the sponge Cacospongia; 4a — scalaradial; 4b — furoscalarol; 4c — deoxoscalarin; Ac — acetyl

Rootmouth jellyfish (order Rhizostomida), particularly those of the genus Rhizostoma, produce a toxic protein called rhysostamin, which causes severe burning pain and respiratory paralysis.

Coral polyps (Class Anthozoa) lead a sessile lifestyle. Horny corals (order Gorgonaria, specifically the genus Lophogorgia) produce lophotoxin, which causes muscular paralysis, ataxia, and Respiratory system impairment.

Sea anemones (order Actiniaria) are mostly solitary animals resembling flowers in shape. The protein equinatoxin has been isolated from the venom extract of the sea anemone Actinia equina, which exhibits cytotoxic activity and causes bradycardia, erythrocyte hemolysis, etc.

Mat anemones (Zoantharia), notably Palythoa toxica, produce palytoxin, a modified fatty acid that promotes histamine release, erythrocyte hemolysis, and contraction of smooth Muscles.

The venom of stony corals (order Madreporaria), particularly Goniopora, contains a polypeptide neurotoxin that induces muscle rigidity and respiratory disorders.

In ribbon worms (phylum Nemertea), the venom apparatus is located within the proboscis, the epithelium of which secretes the toxin. Paranemertes peregrina produces the toxin anabaseine, while Amphiporus angulatus produces its derivatives 2,3'-bipyridyl and nemertilen (Fig. 6.13), which are similar in action to nicotine.

Fig. 6.13. Structure of nemertean toxins from Amphiporus and Paranemertes

These toxins cause paralysis in polychaetes and crustaceans.

The nemertean Cerebratulus lacteus secretes a toxic mucus produced by dermal glands. It contains Polypeptides with cytolytic and neurotoxic activity.

Some marine segmented worms (phylum Annelida) also produce venom, especially polychaetes (Class Polychaeta). They possess chitinous jaws at the border of the Pharynx and buccal region. A pair of venom-producing glands opens into the anterior section of the Esophagus located behind the pharynx. For example, the bloodworm Glycera convoluta produces the neurotoxin α-glycerotoxin, which causes cardiac arrest in Daphnia. The venom of the bristle worm Lumbricineris heteropoda contains the potent insecticide nereistoxin (Fig. 6.14), which primarily affects the insect Nervous system.

Fig. 6.14. Structure of nereistoxin

The organophosphorus derivative of nereistoxin, "cartap" (Bancol), is an effective agent for controlling the Colorado potato beetle and is nearly harmless to birds, fish, rodents, and bees.

Mollusks. Among mollusks (phylum Mollusca), both passively and actively venomous species are found.

Passively venomous gastropods (Class Gastropoda) with venomous digestive glands include mollusks of the families Buccinidae, Turbinidae, Aplysiidae, and Achatinidae, as well as certain nudibranchs of the order Nudibranchia. The venom of Buccinum japonicum causes visual disturbances. It contains surugatoxin (Fig. 6.15), which consists of bromindole, pteridine, and myo-Inositol fragments and acts as a potent ganglionic blocker.

The venom of Turbo argyrostoma and Turbo marmorata is similar in action to saxitoxin and ciguatoxin—dinoflagellate poisons—and results from their bioaccumulation in mollusks along the food chain.

Sea hares, or aplisiids (family Aplysiidae), contain the toxin aplysin, which induces convulsions, ataxia, and respiratory arrest. This toxin and its analogs are produced by red Algae of the genus Laurencia, upon which sea hares feed. Additionally, Other toxins have been discovered in these mollusks—aplysiatoxin (Fig. 6.16) and debromoaplysiatoxin—which cause hyperemia of the nasal and oral mucosa, edema, and delayed healing of skin ulcers.

Fig. 6.15. Structure of surugatoxin

Fig. 6.16. Structure of aplysiatoxin

The digestive gland toxins of certain nudibranchs (Cadlina flavomaculata, Aldisa nobilis [Arisodois nobilis], Doriopsilla albopunctata, etc.) cause bradycardia and hypotension.

Toxins from Achatinidae, particularly Achatina fulica, lead to a decrease in catecholamines and induce narcotic Sleep.

Mollusks with venomous hypobranchial Glands of the genus Murex, specifically Murex brandaris, produce the toxin murexine (Fig. 6.17).

Fig. 6.17. Structure of murexine

Senecioylcholine has been isolated from the hypobranchial glands of Thais floridana, and acrylylcholine from Buccinum undatum (Fig. 6.18).

Fig. 6.18. Structures of senecioylcholine and acrylylcholine

Murexine and its analogues produce effects similar to those of acetylcholine; they induce bradycardia, stimulate respiration and intestinal motility, enhance salivation, etc.

Opisthobranch Molluscs (group Opisthobranchia) secrete mucus containing a sesquiterpene that causes convulsions and loss of coordination.

A typical example of actively venomous gastropods is represented by species of the genus Conus. These are predators that feed on polychaetes, molluscs, and some species, such as Conus geographus, feed on fish.

The venom apparatus of these molluscs consists of a venom bulb, a venom duct, a radula with Teeth, and a proboscis. The mobile proboscis forms the anterior end of the HEAD, holds one of the front radular teeth, and serves to strike the prey. The remaining teeth are arranged in two rows on either side of the radula. The teeth feature channels through which the venom flows from the venom duct, where it is secreted. The venom bulb serves to pump the venom into the tooth channels.

The venom of Conus striatus is a glycoprotein known as striatoxin. It induces paresis, Skeletal Muscle spasms, and respiratory failure culminating in cardiac arrest. It exhibits neurotropic properties. By its MECHANISM OF ACTION, this venom blocks sodium and calcium channels. The active principle of Conus magus venom is a thermolabile protein. It causes convulsions in striated and smooth muscles. In terms of its mechanism of action, this venom increases membrane permeability to sodium ions.

The venom of Conus geographus differs in its action from the venoms of other cone snails. It does not affect the contraction of smooth and cardiac muscle. The active principle of this venom consists of proteins. At relatively high concentrations (12 mg/kg), it exhibits a postsynaptic mode of action, and death results from respiratory arrest.

In Conus californicus, the venom contains a high-molecular-weight protein component that causes the death of vertebrates, and a low-molecular-weight component exhibiting cholinomimetic properties. The primary manifestation of this venom's action is the inhibition of cardiac contraction and the hyperpolarization of Central Nervous System Neurons.

The venom of Conus achatinus contains a protein component that induces cell membrane depolarization and Conformational Changes in muscle cell Membrane Proteins, resulting in increased membrane permeability to sodium and potassium ions.

An individual toxin named eburnetoxin has been isolated from the venom of Conus ebraeus. It induces vascular smooth Muscle contraction. The Mechanism of action of this toxin involves an increase in calcium influx through smooth muscle cell membranes, which triggers their contraction.

The venoms of Conus arenatus, Conus lividus, and Conus quercinus exhibit proteolytic activity. The proteases they contain cause local necrotic lesions.

Actively venomous mollusks include those whose venom is contained in salivary gland secretions, notably Neptunea arthritica and Neptunea intersculpta. The saliva of these mollusks contains the toxin tetramine, which causes impaired motor coordination, nausea, generalized weakness, photophobia, and convulsions.

The saliva of mollusks belonging to the genera Thais and Cassis contains acids that dissolve mollusk shells and echinoderm carapaces, whereas the paralyzing effect of their venom is associated with other components. These induce bradycardia, central nervous system disorders, and vasodilation.

Among mollusks (phylum Mollusca), the most highly organized are the cephalopods (Class Cephalopoda). Their muscular pharynx contains a chitinous beak capable of piercing fish skin, crab carapaces, or mollusk shells. The cuttlefish Sepia officinalis injects venom into the prey's body, which is produced in the posterior Salivary Glands.

The venom of the octopuses Octopus dofleini and Octopus vulgaris, as well as the cuttlefish Sepia officinalis, contains biogenic amines—serotonin, Histidine, tyramine, dopamine, and noradrenaline—along with a toxic glycoprotein called cephalotoxin, which acts as a paralytic poison. Another proteinaceous toxin produced by the posterior salivary glands of the octopuses Eledone moschata and Eledone aldrovandi is eledoisin. The posterior salivary glands of the blue-ringed octopus Hapalochlaena maculosa produce the non-protein neurotoxins maculotoxin and hapalotoxin.

Echinoderms. To a varying degree, venomous organisms among echinoderms (phylum Echinodermata) include sea urchins (Class Echinoidea), sea stars (Class Asteroidea), and sea cucumbers (Class Holothuroidea).

The venom apparatus of sea urchins comprises spines and pedicellariae. The spines are covered with a Glandular Epithelium that secretes venom. When a victim is punctured, the tip of the spine breaks off, releasing the venom into the victim's body. Muscles at the Base of the spines enable them to tilt in various directions. Pedicellariae are homologues of spines with a more complex structure. The venom of the sea urchin Toxopneustes pileolus contains proteins whose mixture is known as urchitoxins. These compounds affect heart rate amplitude, vascular tone and permeability, and smooth muscle contraction.

A proteinaceous toxin has also been isolated from the pedicellariae of Toxopneustes gratilla. It promotes the release of histamine from The Heart, Lungs, and intestines, and causes the degradation of serum a₂-globulins. Its action results in smooth muscle contraction.

The venom from sea urchin spines exhibits certain differences from pedicellaria venom. In addition to proteins that induce smooth muscle contraction, it also contains noradrenaline.

Sea stars, particularly Asterias amurensis, produce asterosaponins A and B, which feature a specific set of sugars. Asterosaponin A is linked via a glycosidic bond to D-quinovose and D-fructose, whereas asterosaponin B is linked to D-quinovose, D-fructose, D-xylulose, and D-galactose (Fig. 6.19).

Fig. 6.19. Structure of asterosaponin B; Fru — fructose, Qui — quinovose, Gal — galactose, Xyl — xylose

Asterosaponins exhibit hemolytic activity and block Nerve Impulse transmission in vertebrate muscles.

A steroid saponin has also been isolated from the starfish Marthasterias glacialis; it acts as a surfactant and toxin on erythrocytes, inducing hemolysis.

Sea cucumbers of the order Aspidochirota possess specialized Cuvierian organs—glandular adhesive tubules that open into the cloaca. When threatened, they can expel these tubules as sticky white threads that entangle and frequently immobilize prey. Holothurian venom is localized not only in the Cuvierian organs but also within the body wall.

Sea cucumbers such as Stichopus japonicus, Cucumaria japonica, and Cucumaria fraudatrix produce cytotoxic triterpene Glycosides known as holotoxins, stichoposides, and cucumariosides. The Chemical Structure of holotoxin B is illustrated in Fig. 6.20.

Fig. 6.20. Structure of holotoxin B (R₁ = D-xylose, R₂ = D-glucose,

R₃ = 3-O-methyl-D-glucose, R₄ = D-quinovose)

Holotoxins and stichoposides exhibit antifungal activity, whereas cucumariosides inhibit nucleic acid and METABOLISM/35.html">Protein Biosynthesis in sea urchin eggs and Saccharomyces Yeasts, as well as altering cell membrane permeability.

ARTHROPOD VENOMS AND ALLOMONES. Among venomous Arthropods (class Arthropoda), the best-studied groups include arachnids (class Arachnida) (scorpions, spiders, and ticks), insects (class Insecta), and myriapods (group Myriapoda).

Scorpions. The order Scorpions (Scorpiones) comprises over 15,000 species. Their segmented metasoma ("tail") terminates in an anal lobe, or telson, which ends in a venomous stinger. A pair of venom glands is located within the telson, with ducts opening near the tip of the stinger via two orifices.

Scorpion venom causes pain, hyperpathia, hyperemia, and edema. Systemic toxic manifestations include thermoregulation disorders, convulsions, muscle tremor, tachycardia, respiratory distress, rhinorrhea, bronchial hypersecretion, impaired consciousness, and frequently myocarditis, pancreatitis, and pulmonary edema.

Several dozen individual polypeptide toxins have been isolated from scorpion venoms. Depending on their specific biological activity, they can be categorized into those affecting mammals, insects, or crustaceans.

Mammal-specific toxins consist of 65–80 amino acid residues, forming compactly folded structures stabilized by Disulfide Bonds. The venom of the Central Asian scorpion Buthus eupeus contains the so-called toxin M₁₀ (Fig. 6.21), which serves as its primary toxic component.

Fig. 6.21. STRUCTURE OF THE M₁₀ polypeptide from the scorpion Buthus eupeus

In terms of its Amino Acid Sequence, toxin M₁₀ shares high Homology with neurotoxin A-II from the venom of Androctonus australis and L-V from Leiurus quinquestriatus.

A mammalian toxin comprising only 32 amino acid residues has been discovered in the venom of the scorpion Scorpio maurus palmatus.

Scorpion insect toxins are subdivided into "short" chains consisting of 35–36 amino acid residues and "long" chains containing 67–70 residues. Similarly, crustacean toxins include a "long" toxin with 69 amino acid residues found in Androctonus australis, and a "short" toxin containing 31–34 residues, such as that found in Scorpio maurus palmatus.

Scorpion venoms contain enzymes typical of other venomous animals, including Hydrolases (phospholipases A and B, acetylcholinesterase, acid phosphatase, 5'-nucleotidase, phosphodiesterase, hyaluronidase, and Ribonuclease).

The most venomous scorpion families belong to Buthidae, Scorpionidae, Vejovidae, and Diplocentridae. Scorpion venom neurotoxins exhibit selective toxicity toward animals of different systematic groups. Insect-specific toxins display the highest degree of Specificity, having no effect on other

animals. Mammalian and crustacean toxins possess a lower relative specificity.

A characteristic feature of venoms from scorpions of the family Buthidae (genera Buthus, Androctonus, Leiurus, Centruroides, and Tityus) is the massive release of Neurotransmitters from postganglionic terminals. This results in cardiovascular and respiratory dysfunction, as well as alterations in blood levels of BIOLOGICALLY ACTIVE SUBSTANCES. Hyperglycemia develops, which promotes Insulin secretion while inhibiting Glucagon production.

Scorpion venom also exerts a direct effect on the Pancreas, leading to enhanced secretion of amylase and Trypsin.

Scorpion neurotoxins are capable of directly affecting the central nervous system. Specifically, α-toxins inhibit the inactivation processes of fast Na⁺ channels in excitable membranes, which leads to membrane depolarization. The binding of α-toxins to the membrane depends on the Membrane Potential and decreases upon membrane depolarization. Scorpion venom β-toxins also modify the activation mechanisms of Na⁺ channels; unlike α-toxins, their binding to membranes is not potential-dependent.

Noxiustoxin, a polypeptide blocker of K⁺ channels, has been found in the venom of Centruroides noxius. The venom of scorpions from the family Scorpionidae contains a cytotoxin known as the "direct lytic factor." It exerts a hemolytic effect that is enhanced by phospholipase A₂.

Some species of these scorpions (in particular, Heterometrus fulvipes) possess a neurotropic venom that induces hyperglycemia associated with increased adrenaline production, whereas in some others (Heterometrus gravimanus) it stimulates acetylcholine, and in yet others (Pandinus exitialis) catecholamine production.

The venom of scorpions from the family Vaejovidae (specifically, Palamneus gravimanus) contains histamine, hyaluronidase, and alkaline phosphatase.

The venom of scorpions from the family Diplocentridae (notably, Nebo hierochonticus) is toxic to both invertebrates and vertebrates, and its action is not related to proteolytic activity. The Effect of this venom manifests as burning pain, erythema, edema, and necrotic changes at the site of the lesion.

Spiders. The order of spiders (Aranei) comprises over 27,000 species, the majority of which are venomous. Spiders of the suborders Mygalomorphae and Araneomorphae are venomous to humans. Spiders seize their prey with chelicerae, which are the first pair of appendages located in front of the Mouth on the ventral side of the cephalothorax. The ducts of a pair of venom glands, situated either in the basal segments or in the cephalothorax, open at the tips of the claw-like segment located at the apex of the outer margin of the main cheliceral segment.

Among Mygalomorphae, the most venomous families are Aviculariidae and Dipluridae. Within the tarantula family Aviculariidae, Representatives of the genera Avicularia, Acanthoscurria, Lasiodora, Pterinochilus, and Poecilotheria pose a danger. For example, the venom of Poecilotheria fasciata causes severe pain and involuntary contractions of the skeletal musculature. It contains histamine and serotonin.

The venom of Pterinochilus sp. also causes severe pain and exhibits a neurotoxic effect. A toxic protein component consisting of 77 amino acid residues has been isolated from it.

The family Dipluridae includes the funnel-web spider Atrax robustus, whose venom causes pain, salivation, lacrimation, tachycardia, Hypertension, release of acetylcholine, and muscle contractions. It contains a toxic polypeptide, atraxin, as well as γ-aminobutyric acid, spermine, and hyaluronidase.

Among Araneomorphae, There are many venomous spiders, particularly those of the families Sicariidae, Theridiidae, Araneidae, Lycosidae, Clubionidae, and Eresidae. In the family Sicariidae, representatives of the genus Loxosceles are the most studied. Their venom causes hemolytic anemia, thrombocytopenia, Blood Coagulation disorders, and renal failure. The venom of Loxosceles (Loxosceles reclusa, Loxosceles laeta, Loxosceles rufescens, etc.) contains hyaluronidase, 5'-nucleotidase, sphingomyelinase, and low- and high-molecular-weight factors. The presence of insectotoxins explains The activity of the venom against insects. The enzymes present in the venom cause lysis of Blood Cells, adipose tissue, and Muscle tissue in invertebrates. In vertebrates, dermonecrosis occurs, and serotonin is released from platelets, leading to their aggregation.

The family Theridiidae, genus Latrodectus, includes the Mediterranean black widow Latrodectus tredecimguttatus. Its venom causes pain, Autonomic nervous system excitation, and psychomotor agitation followed by depression, loss of consciousness, and delirium; death results from bronchospasm and pulmonary edema. In invertebrates, black widow venom causes paralysis. Its composition includes protein-based neurotoxins and enzymes such as hyaluronidase, phosphodiesterase, cholinesterase, and kinase. Among the neurotoxins, α-latrotoxin is the primary active principle. It is a presynaptic toxin that forms channels for Ca²⁺ and certain other ions, thereby promoting the release of neurotransmitters. The venom of black widows is toxic to cattle, horses, camels, rodents, and humans. Dogs, hedgehogs, bats, amphibians, and reptiles are relatively insensitive to it.

Spiders of the species Lityphantes paykulliana produce a neurotropic venom containing an oligomeric toxin that binds to the presynaptic terminal, while another toxin forms channels for Ca²⁺.

Spiders of the family Araneidae include the European garden spider Araneus diadematus, the bolas spider Mastophora gasteracanthoides, and spiders of the genus Nephila.

The venom of Araneus diadematus is toxic to insects and arachnids. In vertebrates, it causes a local inflammatory reaction, hindlimb muscle paresis, labored breathing, and subcutaneous hemorrhages at the bite site. This venom contains a neurotoxin, hemolysin, which blocks synaptic transmission via acetylcholine and glutamatergic synapses in vertebrate and invertebrate animals.

The venom of Mastophora gasteracanthoides causes severe pain and hemorrhagic edema. A potent insecticide is found in the venom of Nephila spiders, particularly Nephila clavata, which blocks glutamatergic synapses. The venom of the spider Argiope lobata exhibits a similar action.

Tarantulas (family Lycosidae) produce a venom that is toxic to both invertebrates and vertebrates. In arthropods, it causes paralysis As a result of disrupted synaptic transmission and membrane depolarization. In mammals, it induces pain, edema, hyperemia, and increased vascular permeability. Tarantula venom, particularly that of Lycosa singoriensis, contains cermin, spermidine, putrescine, cadaverine, and a range of polypeptides and enzymes (hyaluronidase, proteases, esterases, Kinases). The toxicity of tarantulas is seasonal, with maximum toxicity occurring from May to August.

The venom of spiders from the family Clubionidae (Chiracanthium japonicum, Trachelas volutus, etc.) causes burning pain, local erythema, edema, necrosis, respiratory distress, and paralysis. The venom of spiders of the genus Clubiona is toxic to arthropods. In humans, it leads to The Development of lymphadenitis and lymphangitis, Cardiac Arrhythmias, asphyxia, and other complications.

The venom of spiders from the family Eresidae, specifically Eresus niger, causes pain, numbness, and restricted movement.

Ticks. The saliva of certain ticks (order Parasitiformes), particularly Ixodidae and Argasidae, contains venom. For instance, the venom of the castor bean tick Ixodes ricinus, which parasitizes livestock, dogs, and hares and frequently attacks humans, causes epidermal necrosis, lymphocyte infiltration, an increase in the number of basophils, and exhibits anticoagulant properties.

The venom of Ixodes holocyclus causes paralysis, which can be fatal. Species sensitivity to this venom exists; for example, rats are virtually insensitive to the venom of these ticks, whereas dogs are highly sensitive. It poses a serious threat to humans.

Toxic substances from various ticks (Amblyomma hebraeum, Boophilus decoloratus, Boophilus microplus, Rhipicephalus evertsi) produce similar histopathological Changes in the host's tissues—namely, The formation of an exudate that arises from the interaction between tick saliva toxins and host tissues, which serves as a food source for the ticks.

Tick toxins are polypeptides. They are capable of inducing hyperesthesia, anorexia, Conjunctivitis, rhinitis, and hemorrhagic diarrhea. Local necrosis may occur in the liver, along with edema of the Urinary Bladder mucosa and Circulatory Disorders in the lungs, among other effects.

Tick venom, much like that of insects, anemones, and snakes, contains protease inhibitors. These protect protein catalysts from degradation by host proteinases and also provide an anticoagulant effect.

Insect defensive venoms (allomones). Among insects, which number approximately 1,500,000 species, there are both actively venomous and passively poisonous forms. Representatives of the order Hymenoptera—parasitic wasps, bees, wasps, hornets, and bumblebees—possess an armed venom apparatus in the form of an ovipositor or stinger. Most beetles (Coleoptera) store toxic substances in their hemolymph, which they are capable of ejecting over a certain distance. Some species of Lepidoptera possess a primitive wounding apparatus (typically caterpillars), whereas adult butterflies are predominantly passively poisonous. Among dipterans, there are species that inject venom during a bite—horseflies, blackflies, mosquito larvae, and others.

Insects produce venoms that vary widely in Chemical Composition and action. When threatened, they release these venoms to the exterior of the body or eject them over a certain distance. Some beetles, bugs, cockroaches, stick insects, and earwigs are capable of directing a jet of defensive venom toward an adversary and can, to a certain extent, alter the direction of this jet.

Hymenoptera include many venomous insects, such as bees (Apoidea), wasps (Vespoidea, Sphecoidea, etc.), bumblebees (Bomboidae), ichneumon wasps (Ichneumonidae), and ants (Formicoidea).

The stinging apparatus of various Hymenoptera families shares common features. In ichneumon wasps, the ovipositor serves both to lay eggs inside the bodies of other arthropods and to inject venom to paralyze them. In bees, wasps, and some other stinging Hymenoptera, the ovipositor is modified into a stinger used for defense and offense. When stinging, a bee bends the tip of its abdomen downward and strikes with the stinger, driving it into the victim's body. Along with the venom, the bee injects a mixture of isoamyl acetate, isoamyl propionate, and isoamyl butyrate, which act as pheromones that attract other bees to the target.

Bees. After stinging, a bee instinctively tries to fly away, but the stinger, along with the venom glands and the terminal ganglion of the abdominal nerve cord, remains embedded in the victim's skin and continues to function automatically for some time. The bee that loses its stinger dies. Thus, at the cost of the lives of individual insects, the efficiency of the sting is increased, which benefits the bee colony as a whole.

The effects of bee venom can be toxic in nature, caused by multiple stings, or allergenic, which is observed in 2% of people. They may develop anaphylactic Shock in response to even a single sting.

The honey bee Apis mellifera produces venom containing numerous components, the main ones being enzymes (phospholipase A₂, hyaluronidase, phosphatases, α-glucosidase, β-galactosidase), polypeptides (melittin, apamin, tertiapin, secapin, procamine, cardiopep, and mast cell degranulating peptide, or MSD peptide), and biogenic amines (serotonin, histamine, catecholamines). The chemical composition of the venom changes as the bee ages. This unique chemical composition determines the wide spectrum of the venom's physiological effects on nerve cell membranes, The Cardiovascular system, and other organs, producing analgesic and anti-inflammatory effects.

The main component of bee venom, accounting for up to 50% of its content, is melittin. It is a polypeptide consisting of 23 amino acid residues (Fig. 6.22).

Fig. 6.22. Structure of bee melittin

Its primary action is the Modification of the lipid matrix of membranes and, consequently, its effect on membrane-bound enzymes. It is also capable of inducing erythrocyte hemolysis and releasing histamine from mast cells.

Different bee species show some differences in the Introduction/19.html">Primary Structure of melittin; however, overall, the N-terminal sequence between the 1st and 20th amino acid residues is hydrophobic, while the C-terminal sequence between the 21st and 26th is hydrophilic.

Apamin is another component of bee venom that exhibits neurotoxic properties (Fig. 6.23).

Fig. 6.23. Structure of apamin

The MSD peptide (Mast Cell Degranulating Peptide) consists of 22 amino acid residues and two disulfide bonds (Fig. 6.24).

Fig. 6.24. Structure of bee MSD peptide

Tertiapin (Fig. 6.25), which consists of a 21-amino-acid sequence, exhibits a pronounced presynaptic effect.

Fig. 6.25. Structure of tertiapin

Tertiapin inhibits the Ca²⁺-binding protein calmodulin and regulates the activity of several Ca-dependent enzymes.

Bee venom also contains many other substances, notably secapin, which exhibits sedative effects, hypothermia, and piloerection, as well as cardiopep, which significantly enhances Cardiac Activity.

Bumblebee venom (genus Bombus, which make up about half of all apids) is also complex in composition. It contains phospholipases A and B, acetylcholine, histamine, serotonin, and other substances, and exhibits cardiotropic effects.

Wasps. The digger wasps (Sphecoidea) include the European beewolf (Philanthus triangulum), which preys on honey bees. Its venom contains acetylcholine, glutamate, and α-, β-, γ-, and δ-philanthotoxins, which together exert pre- and postsynaptic effects and paralyze honey bees.

Solitary wasps also include spider wasps (Pompiloidea), whose stings, like those of digger wasps, cause mild pain and erythema.

Hornets of the genus Vespa belong to the superfamily of yellowjackets or paper wasps (Vespoidea), which lead a social lifestyle. They build nests from paper that they produce themselves by chewing wood and moistening it with water and sticky saliva.

Their venom causes pain at the sting site, Swelling, general malaise, fever, dizziness, elevated heart rate, and nausea. Allergic reactions may also occur.

The venom of these wasps contains phospholipase A₂, lysophospholipase, histidine decarboxylase, hyaluronidase, DNases, proteases, toxic polypeptides, acetylcholine, histamine, dopamine, norepinephrine, and other substances.

Among the substances found in wasp venom are kinins similar to bradykinin. Some of them are shown in Fig. 6.26.

Fig. 6.26. Structure of some kinins from Polistes wasps

Kinins cause increased vascular permeability and reverse contraction of smooth muscles.

The presence of Biogenic Amines and acetylcholine in the venom explains its effects on the cardiovascular system.

Wasp venom has been found to contain mast cell degranulating (MSD) peptides, which induce mast cell degranulation and are similar to those found in bees. For instance, the MSD peptide mastoparan has been isolated from the venom of Vespula lewisii, and mastoparan X from the venom of Vespa xanthoptera (Fig. 6.27).

Fig. 6.27. Structure of mastoparan and mastoparan X

Wasp venom also contains a number of neurotoxins. For example, neurotoxin E from the venom of Vespa insularis hyperpolarizes the postsynaptic membrane by increasing its chloride conductance. Another typical neurotoxin is mandarotoxin, produced by Vespa mandarina.

Parasitoid wasps. These insects of the family Braconidae, which are endophages, paralyze their victims with venom for only a short period. Soon, the paralyzed insects (caterpillars) begin to move again and resume a normal lifestyle, yet the parasitoid larvae developing from the eggs introduced simultaneously with the venom ensure their own subsequent survival. At the same time, certain parasitoids, particularly of the genus Microbracon, paralyze their prey completely or for a prolonged period.

The active principle of parasitoid venom contains polypeptides. Specifically, the venom of Microbracon hebetor contains protein-nature components A and B, which exhibit presynaptic action. Their Site of Action is the glutamatergic synapses of Lepidoptera and locusts.

Ants. Stinging ants belong to the families Myrmicidae and Poneridae. Relatively potent venom is produced by ants of the genera Solenopsis, Pogonomyrmex, and Myrmecia.

Hemolytic, insecticidal, and antibiotic properties are exhibited by 2,6-dialkylpiperidines, a derivative of which, methyl-2-nonylpiperidine (Fig. 6.28), is produced by ants of the genus Solenopsis.

This venom exhibits neurotoxic activity and blocks the action of acetylcholine at the Neuromuscular Junction. It induces non-specific histamine release from mast cells via a lytic mechanism.

Ants of the species Solenopsis fugax also synthesize trans-2-butyl-5-heptylpyrrolidine, which Functions both as a defensive toxin and as a repellent against other ant species. This compound is also synthesized by certain other ants, notably Monomorium pharaonis.

The venom of Pogonomyrmex ants, particularly Pogonomyrmex badius, is among the most toxic found in insects. It yields a hemolytic polypeptide called barbatolysin, which consists of 34 amino acid residues. Its composition also includes phospholipases A and B, hyaluronidase, acid phosphatase, lipase, and several esterases.

Stings from Myrmecia ants, particularly Myrmecia pyriformis, cause more intense pain than bee stings. They also induce severe itching and erythema that develops into edema.

The venom of these ants contains phospholipase A, hyaluronidase, histamine, hemolysins, and a smooth muscle-contracting factor.

Fig. 6.28. Structure of methyl-2-nonylpiperidine

It should be noted that the ant venoms discussed here do not exhaust all those produced by these insects. The venoms of Myrmecaria natalensis contain monoterpenes, those of Solenopsis punctaticeps contain trans-dialkylpyrrolidines, those of Atta sexdens contain 3-ethyl-2,5-dimethylpyrazine, and many others. Some of these, such as anabaseine in Aphanogaster fulva, have lost their significance as toxins and are instead used by ants as pheromones. Dendrolasin from the ant Dendrolasius fuliginosus exhibits insecticidal properties, while iridomyrmecin possesses both insecticidal and antibiotic activities (Fig. 6.29).

Fig. 6.29. Structure of dendrolasin and iridomyrmecin from ants

Beetles. There are approximately 25,000 known species of Coleoptera, including several venomous ones. The deterrent, irritating, or toxic effects of most venomous beetles are attributed to their hemolymph. When threatened, the hemolymph oozes in droplets onto specific areas of the body surface or is even sprayed over a short distance.

The most toxic among the studied beetles belong to the families Meloidae (Mylabris, Meloe, Lytta, Epicauta) and Staphylinidae (Paederus).

Blister beetles of the genus Mylabris contain the deterrent cantharidin in their hemolymph (Fig. 6.30).

Fig. 6.30. Structure of cantharidin

This poison causes hyperemia of the mucous membranes, liver, and kidneys, impairs conditioned reflex activity, and leads to paralysis. Contact with the skin results in hyperemia, dermatitis, and blistering.

Cantharidin has also been detected in the blood of the Spanish fly, Lytta vesicatoria. In addition to the properties mentioned above, this substance causes severe irritation and serves as the basis for the "Spanish fly aphrodisiac," whose effect on human sexual intercourse is driven by its irritating action on the urogenital organs. Using it is extremely dangerous due to its high toxicity—the lethal dose for humans is 0.5 mg/kg.

The active component in the venom of blue-winged rove beetles of the genus Paederus is the terpenoid pederin (Fig. 6.31), which is capable of inhibiting Protein Synthesis. Ingestion of the venom into the digestive tract causes enteritis.

Fig. 6.31. Structure of pederin

The hemolymph of the Colorado potato beetle, Leptinotarsa decemlineata (family Chrysomelidae), contains a toxic protein called $eta$-leptinotarsin, which affects neuromuscular transmission in vertebrates, inhibits cell growth, and exhibits blister-causing properties. In addition to the hemolymph, this protein is also present in the eggs.

When threatened, ladybird beetles (family Coccinellidae) secrete droplets of hemolymph from their leg joints. This hemolymph contains alkaloids—adaline and concinelline (Fig. 6.32)—which taste bitter to humans and effectively protect these insects from ants and quail.

Fig. 6.32. Structure of concinelline

In some cases, beetles (as well as other arthropods) contain compounds of diverse biosynthetic origins. For instance, the rove beetle Staphylinus olens secretes the terpenoid iridodial and 4-methylene-hexan-3-one, which is formed during the FATTY ACID BIOSYNTHESIS pathway in the beetle's body. This mixture has a very foul odor.

Insects with toxic hemolymph often possess defensive glands whose secretions contain the same toxic compounds found in the hemolymph. For example, the grasshopper Poekilocerus bufonis has a gland on its abdomen that secretes histamine and a series of glycosides.

Diving beetles of the species Ilybius fenestratus synthesize the alkaloid methyl 8-hydroxyquinoline-2-carboxylate (Fig. 6.33), which induces convulsions in mice while remaining non-toxic to amphibians and fish.

Fig. 6.33. Structure of methyl 8-hydroxyquinoline-2-carboxylate

The larvae of beetles from the genus Diamphidia, specifically Diamphidia locusta and Diamphidia nigroornata (family Chrysomelidae), also possess toxic properties. Their venom contains a polypeptide known as diamphidotoxin, which is one of the most potent natural toxins known.

Arthropods (such as beetles, arachnids, centipedes, and termites) widely utilize phenols and Quinones as defensive substances. A striking example of this is The Use of benzoquinone by bombardier beetles of the genus Brachinus. When confronted by a predator, these beetles discharge a hot cloud of toxin that causes severe irritation, primarily affecting the eyes. The Temperature of the toxin reaches 100°C. Its discharge involves a reaction driven by hydroquinone, H₂O₂, and catalase. In this exothermic reaction, hydroquinone is oxidized to benzoquinone, the primary defensive compound. The reaction occurs explosively and is accompanied by a loud pop.

Lepidoptera. In certain species of butterflies and moths (Lepidoptera), both adults and larvae (caterpillars) possess urticating hairs through which venom produced by glandular cells is released.

The most characteristic symptoms of exposure to lepidopteran venom are dermatitis and conjunctivitis. However, in some cases—particularly following contact with the venom of the caterpillar Megalopyge urens—severe pain, bradycardia, convulsions, and nausea may occur.

Based on their origin, the toxic substances of Lepidoptera can be divided into two groups: 1) compounds synthesized by the insects themselves during various phases of their life cycle; and 2) plant-derived compounds that accumulate unaltered in the tissues of larvae and adults, or metabolites of plant compounds. Thus, the order Lepidoptera includes both Primary and secondary venomous moths and butterflies.

Primary venomous Lepidoptera produce a wide variety of toxic substances. For instance, Parasa consocia and several other moth species produce histamine, while Zygaena species produce hydrogen cyanide in addition to histamine. Polypeptides exhibiting trypsin-like, Chymotrypsin-like, and kallikrein-like activities, as well as phospholipase activity, have been discovered in the venom of Euproctis chrysorrhoea and certain other moths. The venom of Parasa consocia contains proteins that trigger severe pain and smooth muscle contraction.

Polypeptide toxins have been identified in Lepidoptera, including their adult (imago) stage. For instance, the toxic polypeptide caiine is isolated from the abdomen of female garden tiger moths, Arctia caja (family Arctiidae). It affects both other insects (such as locusts, cockroaches, and small white butterflies) and mammals, acting as a neuromuscular poison that can induce convulsions and respiratory arrest.

Many lepidopterans are classified as secondary poison-bearing organisms. Examples include danaine butterflies, notably Danais chrysippus. Cardiotropic substances belonging to the cardenolide lipid group have been isolated from adult specimens (both males and females) as well as from eggs. One such compound is uzarigenin, which is toxic to birds that prey on danaines (Fig. 6.34).

Fig. 6.34. Structure of uzarigenin

The cardenolides found in danaines are also present in the Tissues of the plants Calotropis procera and Asclepias curassavica, which serve as food sources for these butterflies. Consequently, these toxic cardenolides are synthesized by plants and accumulated by danaines through food chains.

Insects that inject venom during a bite. These insects lack a stinging venom apparatus. Instead, their venom is introduced into the victim's body

during a bite along with digestive enzymes contained in the saliva. There is no clear-cut boundary between the toxic and digestive components of saliva; for instance, hydrolytic enzymes facilitate the access of toxic substances to cells, while cytotoxins promote their Enzymatic Hydrolysis. The production of venom by salivary glands or their homologs occurs in many animals and reaches its highest evolutionary perfection in snakes.

Among dipterans (order Diptera), the toxicity of salivary gland secretions is most highly developed in the larvae. For example, mosquito larvae of the families Ceroplatidae (genera Platyura and Ceroplatus) and Macroceridae (genus Macrocera) paralyze their prey using venom that contains a relatively high concentration of oxalic acid (up to 0.15%), which is toxic to many other insects.

The venom of Tetanocera plebea and Tetanocera elata larvae causes paralysis in slugs. Another example of a paralyzing venom is found in the saliva of robber fly larvae (family Asilidae), specifically Philonicus dorsiger, which causes respiratory failure and death in other insects, such as the migratory locust Locusta migratoria.

Blood-sucking blackflies (family Simuliidae) inject toxic substances into the wound along with anticoagulants that prevent blood clotting, causing burning sensations, itching, pain, and swelling. Repeated bites can lead to systemic poisoning. Painful bites are also inflicted by adults and larvae of horseflies (family Tabanidae) and robber flies (family Asilidae). The venom of horseflies and robber flies induces paralysis in invertebrates.

The saliva of true bugs (Hemiptera) also possesses toxic properties. For example, the venom of assassin bugs (family Reduviidae) paralyzes invertebrates, and some species produce venom dangerous to mammals. Painful bites are inflicted by bugs belonging to the families Notonectidae (the backswimmer Notonecta glauca) and Nepidae (the water scorpion Nepa cinerea). Giant water bugs of the family Belostomatidae feed on fish fry, tadpoles, and occasionally small fish; their salivary secretions not only paralyze the prey but also liquefy its Internal Organs. Additionally, some bugs contain defensive venoms in their hemolymph, typically composed of several unsaturated aldehydes and n-tridecane. For instance, the venom of the burrowing bug Scaptocoris divergens contains propenal, propanol, octenal, furan, methyl quinone, and other quinones.

The venoms of certain bugs, particularly Triatoma species, trigger allergic reactions in humans.

Net-winged insects (Neuroptera) also produce venoms, but unlike bugs, these are produced by digestive glands. For example, the venom of antlion-like larvae of osmylids (family Osmylidae) paralyzes a much larger chironomid larva within 10 minutes, whereas the venom

of antlions (family Myrmeleontidae) immobilizes its victims within 2 to 4 minutes. The venom of owlflies (family Ascalaphidae), specifically Ululodes mexicanus, paralyzes cockroaches in just 1 second.

MYRIAPOD VENOMS AND ALLOMONES. Myriapods (Myriapoda) comprise four superclasses, of which representatives of the classes Diplopoda (millipedes) and Chilopoda (centipedes) are venomous.

When threatened, millipedes coil into a spiral with their ventral side inward and secrete a venom from numerous pores located on the lateral portions of the body rings' tergites, which emits an unpleasant odor characteristic to humans.

In centipedes, the venom apparatus consists of the poison claws (maxillipeds), each composed of several segments. The terminal segment is pointed and sharply curved inward like a hook. A fine duct of the venom gland runs through this segment; the gland is located within this segment, partially in the preceding one, and, in some species of centipedes such as Scolopendra, extends into the basal segment as well.

The venom of the banded centipede Scolopendra cingulata (superclass Chilopoda) contains acetylcholine, histamine, serotonin, hyaluronidase, cholinesterase, kinase, esterase, and other compounds. Its paralyzing effect is mediated through action on presynaptic nerve terminals.

The centipede Scolopendra morsitrans produces a venom that induces severe hyperglycemia by enhancing Glycogenolysis in the liver and muscles. The hyperglycemic effect of this venom may be attributed to the presence of serotonin, which stimulates the release of adrenaline from the Adrenal Glands, thereby promoting Glycogen breakdown.

The European millipede Glomeris marginata (superclass Diplopoda) synthesizes the quinazoline alkaloids glomerin and homoglomerin, which cause death in spiders and mice that ingest the millipede. Polyzonimin, synthesized by the millipede Polyzonium rosalbum, acts as a local irritant against predatory insects, inducing itching in cockroaches, for instance.

Certain millipedes secrete defensive venoms. For example, Fontinaria gracilis, Fontinaria virginica, and several other species release hydrogen cyanide when threatened, which is generated from a mildly toxic precursor. Millipedes of the species Apheloria corrugata possess 22 pairs of defensive glands containing mandelonitrile. When threatened, these millipedes contract a muscle that forces the venom from the glandular "reservoir" into another chamber known as the "vestibule," where mandelonitrile is enzymatically converted into hydrogen cyanide and benzaldehyde. These substances are then discharged externally to incapacitate predators. In the millipede Glomeris marginata, the defensive venom contains the quinazolines glomerin and homoglomerin (Fig. 6.35), which cause par-

alysis or even death in spiders. Other defensive allomones of myriapods include a series of quinones, p-cresol, iodine, and other substances.

Fig. 6.35. Structure of:

1 — glomerin (R = СН₃) and homoglomerin (R = С₂Н₅); 2 — polyzonimin

The millipede Apheloria corrugata, besides soluble poisons, releases a pair of hydrogen cyanide streams for several minutes after being disturbed. This acid, along with benzaldehyde, is formed during the enzymatic breakdown of a substance called mandelonitrile, immediately prior to its release from the poison gland.

FISH POISONS (ALLOMONES). Among the classes of cartilaginous fish (Chondrichthyes), which number about 630 species, and bony fish (Osteichthyes), which exceed 20,000 species, there are venomous species. They can be divided into actively venomous and passively venomous. The former possess both mucous skin poison glands and a wide variety of spines and prickles, which often contain specialized venomous glands that likely originated from mucous poison glands.

Other venomous fish contain poison in their muscles, skin, and internal organs, particularly the Gonads. It is hardly a coincidence that poison concentration in such fish peaks during the spawning season. Thus, passively venomous fish defend themselves through poison at the cost of individual predators consuming some specimens, thereby ensuring the survival of the population.

A representative of cartilaginous actively venomous fish is the spiny dogfish, or spiny shark Squalus acanthias. The tip of the spine is bare, while the lower part is covered by a skin sheath beneath which poison glands are located. The venom is proteinaceous in nature and causes skeletal muscle paralysis and paresis in animals and humans.

Cartilaginous venomous fish also include stingrays, specifically the common stingray Dasyatis pastinaca, the giant freshwater stingray Urolophoides giganteus, and others. The poison glands are located in the grooves On the surface of the spine, which is situated in the middle part of the tail. The venom is proteinaceous in nature, causing edema, convulsions, respiratory and cardiac disorders,

as well as a drop in blood pressure. Usually, an affected person recovers within 5 to 7 days, but punctures to the chest or abdomen can be fatal.

An actively venomous bony fish is the greater weever Trachinus draco, in the grooves of whose dorsal fin spines lie venomous glands covered at the base by a sheath, while the sharp spines remain bare. The venom has been found to contain albumins, Polysaccharides, glycoprotein complexes, serotonin, histamine, cholinesterase, and other compounds. At the site of the puncture, edema appears, the wound reddens, and tissue necrosis develops. A burning sensation is felt, accompanied by headache, severe sweating, cardiac and respiratory disorders, possible limb paralysis, and in the most severe cases, death. In most cases, poisoning symptoms subside within 2 to 3 days.

Rockfish, particularly the yellow Irish lord Sebastes trivittatus, the Pacific ocean perch Sebastes alutus, and the golden redfish Sebastes marinus, have a venom apparatus structure similar to that of the greater weever Trachinus draco, but their dorsal fin is T-shaped. The venom is proteinaceous in nature and causes impaired coordination, respiratory difficulties, and cardiac dysfunction.

Another venomous bony fish is the black scorpionfish, or sea ruffe Scorpaena porcus. The venom is injected during punctures by the spines of the dorsal, pelvic, and anal fins. It is proteinaceous in nature, causes severe pain, impairs respiration and cardiac activity, and sometimes leads to limb muscle paresis.

Passively venomous fish include, in particular, representatives of the carp family (Cyprinidae), including osmans (Schizothorax), snowtrouts (Diptychus), and barbels (Barbus), in which the roe and milt are toxic. They contain so-called ichthyotoxins, the component of which is cyprinidin. These poisons cause adynamia, hypothermia, hypotension, cardiovascular and respiratory disorders, skeletal muscle paralysis, and, in large doses, cardiac arrest.

From the ichthyotoxins of Stichaeus grigorjewi, the toxic lipoprotein dinoineulin (also known as liposticharin) has been isolated. Toxic substances are also found in the roe of many other fish species.

Toxic properties are also present in the Bile of the grass carp Ctenopharyngodon idella, which induces diuresis and bradycardia.

Fish of the pufferfish family (Tetraodontidae), comprising about 90 species and also known as toadfish or fugu, contain tetrodotoxin (Fig. 6.36). This compound consists of aminoperhydroquinazoline with a guanidine group. The lethal dose of tetrodotoxin for humans is 1 • 10 mg/kg. In its potency, this poison exceeds curare by 10 times and strychnine by more than 400 times.

Fig. 6.36. Structure of tetrodotoxin

Despite its toxicity, in Eastern countries (primarily Japan), fugu is considered a delicacy, and specific preparation Methods exist. The most toxic parts are the gonads and liver, while the skin and intestine are slightly less toxic. The toxicity of this fish exhibits seasonal fluctuations, peaking during the spawning season from May to July.

Tetrodotoxin is capable of being rapidly absorbed into the bloodstream and penetrating various biological barriers of the body, accumulating primarily in the kidneys and heart.

The first symptoms of tetrodotoxin poisoning appear anywhere from a few minutes to 3 hours after consuming the fish. Sometimes death can occur within the first hour, but typically within 4 to 6 hours. The initial sign of poisoning is tingling and numbness of the Tongue, loss of its mobility, as well as numbness in the tips of fingers and toes. Numbness can spread throughout the entire body. This is followed by pain in the head, abdomen, and limbs. Progressive decreases in vascular tone and blood pressure, respiratory depression, skeletal muscle paralysis, and a drop in body temperature ensue. The patient lapses into a coma, and shortly after the loss of consciousness, respiratory arrest and death occur.

The toxic action of tetrodotoxin is based on its ability to block Nerve Impulse Conduction in excitable tissues. The uniqueness of its action lies in its ability, even at low concentrations (1(Г⁷ mol/L), to block the outward sodium current during the Development of the Action Potential.

At certain low doses, tetrodotoxin is used as a potent analgesic for severe forms of leprosy, inoperable Cancer, and other conditions.

Tetrodotoxin has been detected in the tissues of several invertebrates, including the mollusk Charonia sauliae; sea stars Astropecten polyacanthus and Astropecten scoparius; crabs Atergatis floridus and Zosimus aeneus; the blue-ringed octopus Hapalochlaena maculosa; and certain other marine invertebrates. It has also been found in newts of the genus Taricha (e.g., Taricha torosa) and frogs of the genus Atelopus.

It is believed that this toxin enters the bodies of herbivorous fish, such as Scarus gibbus, and crabs via the red alga Tania sp., which they consume as food. Additionally, tetrodotoxin is contained in Bacteria of the genus Pseudomonas present on this alga. Therefore, this toxin may be of bacterial origin.

Passively venomous fish also include members of the boxfish family (Ostraciontidae), which comprises 7 genera and about 20 species. Typical representatives include trunkfish such as Acanthostracion quadricornis, Ostracion lentiginosum, Terasomus gibbosus, and others.

If boxfishes are placed in an aquarium, the toxins they release into the water can kill other fish. Toxins and their armor do not fully protect boxfishes, as they are frequently found in the stomachs of predatory fish.

A number of other toxins have been discovered in fish. For example, goatfishes such as Upeneus arge and Mulloidichthys samoensis contain a poison that causes hallucinations, nightmares, muscular weakness, and partial leg paralysis in humans. Symptoms appear within a few minutes to 2 hours and can last from 5 to 24 hours. Poisoning is caused by both raw and cooked fish. Toxicity peaks during the spawning period in July and August.

Hallucinations also occur after consuming the mullets Mugil cephalus and Neomyxus chaphalli.

Consuming so-called "sleeper fish," particularly Kyphosus vaigiensis, likewise induces hallucinations and nightmares in humans, followed by prolonged sleep.

AMPHIBIAN ALLOMONE POISONS. This class of vertebrates comprises over 4,000 species, among which a number of anurans (Anura) and urodeles (Caudata) include venomous representatives. These animals are classified as unarmed, actively venomous. Their venom apparatus lacks delivery devices (spines, stingers), nor do they possess venom glands associated with the mouthparts, as observed in snakes.

The production of poisons by amphibians serves a defensive function. The toxin is synthesized by specialized alveolar skin mucous glands.

The venom from such glands produces toxic effects upon contact with the skin. The primary active constituents of the poison are steroidal alkaloids, which resist degradation by digestive enzymes when ingested orally.

The venom of the urodele spotted salamander (Salamandra) includes steroidal alkaloids such as samandarin (Fig. 6.37), samandaron, cycloneosamandaron, and others, as well as serotonin and hemolytic proteins.

Fig. 6.37. Structure of samandarin

Salamander poison can be absorbed through intact mucous membranes. It exhibits neurotoxic, cardiovascular, antibacterial, and antifungal activities.

Toads of the genus Bufo belong to anurans. The most widespread is the common toad, Bufo bufo. Smaller in size are the European green toad (Bufo viridis) and the natterjack toad (Bufo calamita). Toad skin contains numerous poison glands, most notably two large suprascapular (parotoid) glands.

Toad venom contains a range of compounds (around 100), the most potent being bufotenin—a dimethyl derivative of tryptamine (N,N-dimethyl-5-hydroxytryptamine) (Fig. 6.38)—bufadienolides (cyclopentanoperhydrophenanthrene derivatives containing a lactone ring in their molecular structure), and batrachotoxin (an ester of 2,4-dimethylpyrrole-3-carboxylic acid).

Fig. 6.38. Structure of bufotenine

In addition to these, toad venom contains a number of other compounds, such as tryptamine, serotonin, bufotenine ether, bufotenidine, bufadienolide homologs (cardiolipins), catecholamines, endorphins, and phospholipase A₂.

Venoms of different toad species have distinct compositional features. For instance, the venom of the European green toad contains resibufogenin, but lacks bufotemidin, which is found in the venom of the common toad.

Toad venom exhibits a wide spectrum of biological effects, including circulatory and respiratory disorders, convulsions, limb paralysis (in mice, rats, and rabbits), cardiovascular dysfunction (in dogs), and limb paralysis (in amphibians).

Fire-bellied toads (specifically, the European fire-bellied toad Bombina bombina and the oriental fire-bellied toad Bombina orientalis) belong to the order of tailless amphibians (Anura). Their venom contains bufotenine and bufotenidine, the polypeptide bombesin (Fig. 6.39), a hemolytic protein, and potentially other compounds.

Fig. 6.39. Structure of bombesin

The venom of fire-bellied toads causes erythropenia, a decrease in Hemoglobin concentration, and a strong stimulatory effect on gastrin secretion.

Tailless amphibians also include the common spadefoot toad (Pelobates fuscus), whose Skin glands secrete a venom with a distinct garlic odor. It is toxic to small animals and causes irritation of mucous membranes in humans.

SNAKE ALLOMONE VENOMS. There are approximately 3,000 known snake species, of which nearly 230 are venomous.

In most snakes, venom glands are modified salivary glands—specifically, the upper labial and temporal glands. These glands open into specialized teeth located at the anterior or posterior end of the upper jaw. The venom enters the grooves or canals of these fangs. During a bite, the venom flows down the fangs into the victim's body. Some snakes are capable of forcefully expelling air over a considerable distance, carrying along the venom flowing down their fangs.

Snake venom is a complex mixture of substances. These include pre- and post-synaptic toxins, cardiotoxins, myotoxins, hemorrhagic toxins, and Proteolytic Enzymes, which are highly toxic to humans. Less toxic components include phospholipases, anticoagulants, and a range of enzymes such as phosphodiesterases, acetylcholinesterases, and NAD-nucleosidases. Among the proteolytic enzymes, Endopeptidases, isopeptidases, collagenases, and elastases have been identified.

Certain components of snake venoms, particularly various enzymes (such as phospholipase A₂, hyaluronidase, and oxidase), are common to the venoms of different snake families. At the same time, others are specific to particular families. For example, the venoms of elapids and sea snakes contain neurotoxins that disrupt excitation transmission at neuromuscular junctions, thereby causing paralysis of the skeletal and respiratory musculature. These venoms contain acetylcholinesterase. Conversely, the venoms of vipers and pit vipers lack acetylcholinesterase, but are rich in enzymes with trypsin-like, Thrombin-like, and kallikrein-like activities.

Proteroglyphous snakes ("poisonous" fangs located on the anterior edge of the Maxilla) include the Central Asian cobra, vipers (common, steppe, Caucasian, sand viper), pit vipers (northern snake, eastern pit viper), etc.

The venom of the Central Asian cobra Naja oxiana (family Elapidae) comprises neurotoxins (Fig. 6.40), cytotoxins, proteins with specific functions (nerve growth factor, anticomplementary factors, etc.), and a number of enzymes: acetylcholinesterase, phospholipase A₂, endoribonuclease, deoxyribonuclease, phosphodiesterase, 5'-nucleotidase, L-Amino Acid Oxidase, hyaluronidase, etc.

Allomone venoms of lizards. Among lizards (Sauria), numbering about 3,500 species, only 2 families are venomous—the Gila monster family (Helodermatidae) and monitor lizards (Varanidae).

Gila monsters are represented by 2 species: the Gila monster (Heloderma suspectum) and the beaded lizard (Heloderma horridum). Their venom is produced by infralabial glands located laterally on the lower front half of the Mandible. Through several ducts, it flows to the outer side of the largest grooved teeth of the lower jaw.

The venom contains L-amino acid oxidase, hyaluronidase, phospholipase A₂, Arginine esterase, serotonin, and other substances.

The bite site develops edema, accompanied by weakness, dizziness, respiratory disorders, lymphadenitis, and thrombocytopenia.

Monitor lizards include 30 species. Their bite is accompanied by an inflammatory reaction and severe pain. There is evidence that the venom is present in saliva and is capable of immobilizing prey.

Allomone venoms of birds. Until recently, the existence of birds capable of producing and secreting venom was questioned. However, in New Guinea, birds such as Pitohui dichrous, Pitohui ferrugineus, Pitohui kihocephalus, and Ifrita kowaldi have been discovered that produce the steroidal alkaloid batrachotoxin. As already noted, this is one of the most potent natural non-protein toxins. It is also produced by certain animals, notably frogs of the genus Phyllobates.

The venom is secreted by birds from glands located on the ventral side of the body. To get rid of parasites and predators, the bird crawls through the nest and smears it with venom. A bird weighing 60 — 65 g produces up to 15 — 20 mg of venom, with 2 — 3 mg contained in the feathers. The lethal dose of batrachotoxin for a 20 g mouse is 0.03 mg. The secretion of venom by the aforementioned birds is evidently an adaptation for defense against predators.

MAMMALIAN ALLOMONE VENOMS. The presence of venom is uncharacteristic of mammals (Mammalia). This can be explained by the fact that with the high evolution of The Nervous System and effective defense mechanisms, the production and secretion of venom became unnecessary. At the same time, among egg-laying mammals (monotremes) Prototheria and live-bearing Theria, there are isolated venomous representatives.

Fig. 6.40. Structure of neurotoxin I (a) and neurotoxin II (b) of the Central Asian cobra

Egg-laying mammals are grouped into families: platypuses (Ornithorhynchidae) with a single genus Ornithorhynchus, and echidnas (Tachyglossidae) with five species. In the platypus and echidna, the venom apparatus is localized in the femoral gland, which is connected via a duct to a spur located on the inner side of the hind limb. Only males have a developed spur; in young females, the spur is rudimentary, and in sexually mature females, it is absent.

Venom toxicity is seasonal, reaching its maximum in June before the onset of sexual activity. It is proteinaceous in nature, thermolabile, causes Blood Plasma coagulation in the absence of calcium, and lacks proteolytic and hemolytic enzymes. Human envenomation results in edema and cardiovascular disorders. No fatal cases in humans have been reported from this venom.

Among live-bearing mammals, venomous species belong to the Order Insectivora, representing two families: solenodons (Solenodontidae) and shrews (Soricidae). The saliva of certain species of these animals exhibits neurotoxic activity.

Solenodons are represented by 2 species: Solenodon paradoxus and Solenodon cubanus. They feed mainly on various invertebrates and small vertebrates, and are also capable of consuming certain plants.

Shrews are represented by approximately 250 species. Their primary diet consists of insects. The saliva of some species is venomous, particularly to amphibians. It is possible that the toxicity of the salivary gland secretion in solenodons and shrews is an adaptation for hunting agile prey that is large relative to these animals.

Venom has been discovered on the quills of porcupines (Hystriacidae), which apparently serves a defensive function.

BIOLOGICAL BEHAVIOR OF ANIMALS REGARDING THE VENOMS THEY PRODUCE. Predatory animals typically possess an armed venom apparatus (snakes, scorpions, spiders, sea anemones, wasps, etc.). Their venom has a pronounced neurotropic effect, as it is primarily intended to immobilize prey. Often, the neurotropic action of such venoms is characterized by high selectivity. For example, scorpion venom contains species-specific neurotoxins that selectively affect insects, crustaceans, and mammals, while the venom of braconid wasps is primarily active against Lepidoptera. Predator venom is also used for active defense.

In animals with an unarmed venom apparatus, venom is produced primarily for defense, with deterrence being one such mechanism. For instance, repellents are produced by amphibians, centipedes, beetles, ants, etc. Among mammals, some badgers, the striped skunk (Mephitis mephitis), and the Molina's hog-nosed skunk (Conepatus suffocans) use foul-smelling compounds to deter enemies. When they spot an enemy, they turn their rear toward it and spray a stream of fluid containing foul-smelling mercaptans through the anus.

It should be noted that the action of allomone venoms is relative. It does not affect all animal species, but only specific ones. Snakes, scorpions, and spiders possess venoms with the broadest range of action. At certain doses, they can rapidly kill most vertebrates, while only isolated animal species are less or more slowly susceptible to such venoms.