Animal toxins

Some species from practically all phyla of animals produce toxins for either offensive or defensive purposes. Some are passively venomous, often following inadvertent ingestion, whereas others are actively venomous, injecting poisons through specially 

Snake venoms have been studied extensively their effects are due, in general, to toxins that are peptides with 60 to 70 amino acids. These toxins are cardiotoxic or neurotoxic, and their effects are usually accentuated by the phospholipases, peptidases, proteases, and other enzymes present in venoms. These enzymes may affect the bloodclotting mechanisms and damage blood vessels. Snake bites are responsible for less than 10 deaths per year in the United States but many thousand worldwide. 

Many fish species, over 700 species worldwide, are either directly toxic or upon ingestion are poisonous to humans. A classic example is the toxin produced by the puffer fishes (Sphaeroides spp.) called tetrodotoxin (TTX). Tetrodotoxin is concentrated in the gonads, liver, intestine, and skin, and poisonings occurs most frequently in Japan and other Asian countries where the flesh, considered a delicacy, is eaten as fugu. Death occurs within 5 to 30 minutes and the fatality rate is about 60%. TTX is an inhibitor of the voltage-sensitive Na channel (like saxitoxin) it may also be found in some salamanders and may be bacterial in origin. 

Toxins and other natural products generally provide great benefit to society. For example, some of the most widely used drugs and therapeutics like streptomycin, the aminoglycoside antibiotic from soil bacteria, and acetylsalicylic acid (aspirin), the nonsteroidal anti-inflammatory from willow tree bark, are used by millions of people everyday to improve health and well-being. On the other hand, adverse encounters with toxins like fish and shellfish toxins, plant, and insect toxins do result in harm to humans. 

Histamine Pain, vasodilation, increased capillary permeability 

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Nature has created a diverse array of plant and animal toxins that act at mammalian muscle and ganglionic nAChRs or invertebrate nAChRs because the critical physiological functions of these receptors make them prime targets for defensive or predatory strategies. More recently, the perceived validity of neuronal nAChR as therapeutic targets has prompted the generation of new synthetic ligands. Examples are listed in Table 1. 

Dauplais, M., Lecoq, A., Song, J., Cotton, J., Jamin, N., Gilquin, B., Roumestand, C., Vita, C., de Medeiros, C.L.C., Rowan, E.G., Harvey, A.L. and Menez, A. (1997) On the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures. Journal of Biological Chemistry 272, 4302 309. 

Figure 1 3-Dimensional structures of the most common animal toxin scaffolds. Different types of fold of toxins from various animal species are shown (a) /3/3/3 (b), and (c) two types of aa (d) 3io/3/3 (e) a/3/3, (f) 3ioaa (g) /3a/3/3 (h) (i) /3/3 (j) /3/3/3/3 ...

Besmajouirou has a Ph.D. in neurosciences. She is affiliated to the ERT 62 laboratory and holds a position as a researcher in a biopharmaceutical company. She works in the field of animal toxins, antitumor compounds, and antivirals. She has contributed to 10 scientific articles, 6 communications, and 2 patents. 

Jean-Marc Sabatier has a Ph.D. and HDR in biochemistry. He is the director of research at the French Centre National de la Recherche Scientifique (CNRS). He heads a research laboratory (ERT 62) entided Engineering of Therapeutic Peptides at the Universite de la Mediterranee, in Marseilles, France. He also holds the position of a senior director (discovery research — peptides) for a public company in Canada. Dr. Sabatier works in the field of animal toxins, and leads the venom peptide group of the International Neuropeptide Society. He also designs immunomodulatory and antiviral drugs, as well as contributes to the field of peptide and protein engineering. He has contributed more than 100 scientific articles, 180 communications, and 43 patents. He is a member of several scientific advisory boards of journals (e.g.. Peptides, Biochemical Journal), and has reviewed articles submitted for publication in more than 30 specialized international journals. 

We gratefully acknowledge the continued support of our research on animal toxins by the National Institutes of Health (most recently NIH NS14345-06). The ideas we have developed here would not have evolved without this sustaining aid for our collaborative efforts. 

Animal toxins are roughly divided into venoms and poisons. Venoms are offensive, used in the quest for food. Snakes produce toxins that can immobilize or kill prey for food. The venom of spiders paralyzes insects to allow the spider to feed on the victim s body fluids. While the venoms may also be used defensively, their primary purpose is in the quest for food. Most venom is delivered from the mouth, as in snakes and spiders, but there are exceptions like the scorpion that uses its tail. 

ANTITOXIN. (1)A substance made and elaborated in the body to neutralize a specific bacterial, plant, or animal toxin (2) one of the class of specific antibodies. See also Antibody. 

Silva AM, Liu-Gentry J, Dickey AS et al (2005) a-Latrotoxin increases spontaneous and depolarization-evoked exocytosis from pancreatic islet P-cells. J Physiol 565 783-99 Siu R, Fladd C, Rotin D (2006) N-cadherin is an in vivo substrate for PTPo and partidpates in PTPo-mediated inhibition of axon growth. Mol Cell Biol 27 208-19 Smith DS, Russell FE (1966) Structure of the venom gland of the black widow spider Latrodectus mactans. A preliminary light and electron microscopic study. In Russell FE, Saunders PR (eds) Animal Toxins, Oxford, Pergamon, pp 1-15... 

Our coverage includes bacterial, plant and animal toxins and we focus mainly on the period from approximately 2003 onwards, with some early examples also included for historical perspective, or for completeness in defining the scope of structures determined. For the examples we describe in more depth, there is an emphasis on studies from our laboratory, but these are illustrative of a wide range of studies from other laboratories. Our laboratory has had a particular interest in peptides that have head-to-tail cyclised backbones and so a number of the examples fit this theme. 

The controversy over the connectivity does highlight the fact that the determination of disulphide connectivities in disulphide-rich peptides is notoriously difficult and caution needs to be exercised in using solely NMR methods to determine disulphide connectivity. Isotopic labelling approaches116 have been recently used for conotoxins, a disulphide-rich class of animal toxins that are described in more detail later in this article. 

How can this scattered taxonomic occurrence of the picrotoxanes be explained Many of the apparent chemical convergences in animal toxins have been explained as toxins received via the food chain e.g. brevetoxin, pederin, saxitoxin, tetrodo-toxin, and the toxins of the arrow-poison frogs). This may explain the occurrence of picrotoxanes in both parasitic animals and plants, but further research will be necessary for a better understanding of this phenomenon. 

Between October 30 and November 4, 2000, 11 persons were intoxicated due to ingestion of a serranid fish Epinephelus sp. in Kochi Prefecture, Japan. Their symptoms included severe muscle pain, low back pain, and discharge of black urine. The causative agent was identified as palytoxin on the basis of delayed haemolytic activity, which was inhibited by an anti-palytoxin antibody and ouabain (Taniyama et al. 2002). Although the toxic dose of palytoxin in humans could not be determined, extrapolation of the data available in animals will give a toxic dose in a human of about 4 pg. This fact places palytoxin among the most toxic nonproteinic animal toxins known to date (Taniyama et al. 2002) however, its mechanisms of toxicity remain to be elucidated. 

Karalliedde L (1995) Animal toxins. British Journal of Anaesthesia 74 319-327. 

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