Cytotoxic venoms

Loxosceles venom contains hyaluronidase, alkaline phosphatase, 5-ribonucleotide phosphohydro-lase, and sphingomyelinase D. Sphingomyelinase D is a component of the cytotoxic venom, with a MW of... 

CTL Cytotoxic T lymphocyte CTLA-4 Known to be co-expressed with CD20 on activated T cells CTMC Connective tissue mast cell CVF Cobra venom factor... 

Since predators of snakes (and humans) have to deal with snake venoms as defenses, they are included here, even though they serve in predation. Snake venoms are primarily enzymes (proteins), especially of the phospholipase A2 type, which breaks down cell membrane phospholipids hydrolytically. Other snake venoms such as cobrotoxin contain peptides with 60-70 amino acid residues. Pharmacologically, they have neurotoxic, cytotoxic, anticoagulant, and other effects. The neurotoxins, in turn, can have pre- or postsynaptic effects. Snake venoms with both neurotoxic and hemolytic effects on the heart are known as cardiotoxins. Cytotoxins attach to the cells of blood vessels and cause hemorrhage. Snake venom factors may stimulate or inhibit blood clotting. Finally, platelet-active factors can contribute to hemorrhage. 

Histamine may be released from mast cells by mechanisms that do not require prior sensitization of the immune system. Drugs, high-molecular-weight proteins, venoms, and other substances that damage or disrupt cell membranes can induce the release of histamine. Any thermal or mechanical stress of sufficient intensity also will result in histamine release. Cytotoxic compounds, may release histamine as the result of disruption of cell membranes. 

One of the most well-known examples of insect toxins is melittin, a bee venom peptide with potent haemolytic activity. Melittin adopts an a-helical conformation, and has been extensively characterised using a range of techniques, including both solution- and solid-state NMR spectroscopy.176 Some helical peptides with antimicrobial activity have also been found in wasps, such as eumenine mastroparan-AF (EMP-AF-NH2) from the venom of the solitary wasp Anterhynchium flavormarginatum micado,177 and the cecropins found in the haemolymph of Hyalophora cecropia.178 Several of these peptides have cytotoxic activity and are potential anticancer agents.179... 

Iwli et al [97] have reports based on the evaluation of plant-extract of D. multiradiata for antileishmanial activity using a mechanism-based radiorespirometric micro-technique. Extracts were found to be active at concentrations of 50 pg/ml or less against a visceral leishmania isolate. A number of Dorstenia species used traditionally as anti-snake venom were subjected to a pharmacological screening process and were found to possess analgesic and anti-inflammatory activities [98]. Many of the flavonoids isolated from African Dorstenia show moderate to good antioxidant activities [Croft, unpublished results]. The cytotoxic properties of... 

Envenomation from a coral snake exerts minimal local pain, and appears as rows of teeth marks. Victims may report that the snake was chewing on the bite site and had to be forcibly removed. Coral snake venom is composed of peptides and enzymes that have not all been identified, but which exert neurotoxicity rather than cytotoxicity. 

Presynaptic toxins - polypeptide snake venoms This group contains multimeric polypeptides containing subunits with phospholipase Aj activity, and often contains other subunits with a chaperone role. Toxicity does not normally rest on enzyme activity alone, and binding may occur other than on neuronal tissue, e.g. some cause skeletal muscle cytotoxicity. Examples from snake and viper venoms include agkistrodotoxin, ammodytoxin A. P-bungarotoxins. mojave toxin, notexin. taipoxin and textilotoxin. 

When 5 -0-tritylthymidine-3 -phosphate is treated with excess tri-isopropyl benzenesulphonylchloride (TPS) and thymidine, and then deprotected, the trinucleoside monophosphate (7a) is obtained. The 5-bromo- and 5-fluoro-deoxyuridine analogues (7b) and (7c) are prepared similarly. All are resistant to snake venom and spleen phosphodiesterases, and hydrolyse too slowly under physiological conditions for the cytotoxic moiety to be effective. When protected UpU is treated with bis-(4-nitrophenyl) phosphorochloridate, and subsequently with an amine or amino-acid ester, the dinucleoside phosphor-amidates (8) are formed. Although the compounds investigated split the P—N bond under the conditions required for protecting-group removal, the method has potential for the preparation of easily fissionable neutral phospho-triesters. 

A modified version of the Computer Automated Structure Evaluation (CASE) program has been successfully applied to the study of the neurotoxic and cytotoxic activity of the snake venom toxins. The program identified the sites that seem to be the most relevant to the activity of these two classes of peptides. The knowledge of the three dimensional structure of these peptides together with the relevant fragments selected by the CASE program helped to clarify the differences between the activity of each type of toxin. 

Resibufogenin, (30,50,150>-I4,ls-Epoxy-3-kydr-oxy-5-bufa-20,22-dienolide Respigon. CMHJ204 mol wt 384.50. C 74.97%, H 8.39%, O 16.65%. Cytotoxic constituent of toad venom. Isoln Meyer, Helv. Chim, Acta 35, 2444 (1952) Linde, Meyer, Pharm, Acta Helv. 33, 327 (1958). Structure Thiessen, Chem. Ind. (London) 1988, 440 ... 

Causes of rhabdomyolysis include prolonged immobilization on a hard surface, excessive seizures or muscular hyperactivity, hyperthermia, or direct cytotoxic effects of the drug or toxin (eg, carbon monoxide, colchicine. Amanita phalloides mushrooms, and some snake venoms). 

B. Loxosceles (brown spiders) venom contains a variety of digestive enzymes and sphingomyelinase D, which is cytotoxic, chemotactically attracts white blood cells to the bite site, and also has a role in producing systemic symptoms such as hemolysis. 

Although many cationic peptides are antimkrobial to some extent, their propensity to be toxic to mammalian cells varies greatly. For example, Schluesener et al. (85) found that although indolicidin and, to a lesser extent, bactenecin are strongly cytotoxic to T lymphocytes, the defensins HNP-1, HNP-2, and HNP-3 did not affect the proliferation or viability of the T lymphocytes. On the other hand, the cationic peptides melittin and charyldotoxin are the potent toxins of bee and scorpion venom, respectively. 

Such interactions with other membrane components could certainly provide an attractive basis for the specificity of some peptides that appear to have a similar general structure. This situation might then be analogous to that of a group of structurally related peptides from snake venom which have separate defined regions that are responsible for either cytotoxicity or neurotoxin activity 28),... 

In nature, the art of chemical warfare may have reached its zenith with the innovation of venomous animals, those that not only contain poisonous toxins but also have the anatomical apparatus to inject those toxins directly into other animals. Venoms come in four different types cytotoxic, causing cell death proteolytic, dismantling the molecular structure around the area of the injection hemotoxic, causing failure within the cardiovascular system or neurotoxic, acting on the nervous system and the brain. 

An Ultrastructural Study of the Cytotoxic Effect of the Venoms from the... 

Mariottini, G.L., Sottofattori, E., Mazzei, M., Robbiano, L., and Carli, A. (2002) Cytotoxicity of the venom of Pelagia noctiluca Forskal (Cnidaria Scyphozoa). Toxicon, 40, 695-698. 

B. Muller, and W. Muller-Ruchholtz. Covalent conjugates of monoclonal antibody and cobra venom factor mediate specific cytotoxicity via alternative pathway of human complement activation. Leukemia Res. 11,461-468. 

H. Juhl, E. C. Petrella, N.-K. V. Cheung, R. Bredehorst, and C.-W. Vogel Complement killing of human neuroblastoma cells A cytotoxic monoclonal antibody and its F(ab )2-cobra venom factor conjugate are equally cytotoxic. 1990. Mol. Immunol. 27, 957-964. 

Chiou, S., Raynor, R.L., Zheng, B., Chambers, T.C., and Kuo, J.F., 1993, Cobra venom cardiotoxin (cytotoxin) isoforms and neurotoxin Comparitive potency of protein kinase C inhibition and cancer cell cytotoxicity and modes of enzyme inhibition. Biochemistry 32 2062-2067. 

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