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A cautionary note on the interpretation of data concerning oral products of lizards1 www.toxinology.com

The recent detection in several lizard oral products of polypeptide or transcript classes common in snake venoms (e.g. Fry et al., 2006, 2009, 2012) has stimulated renewed attention to the origin of squamate reptile venoms. Although the presence of these biologically active proteins and toxins provide fertile ground for research regarding their origin, their basic biological functions are unclear. Therefore, it is not currently ascertained if these substances are a consequence of pre-adaptation (recruitment of previously existing proteins for a later role in the organism’s natural history), or if they provide a specific selective advantage in survival. Speculation about possible roles of these oral products must be investigated with caution as premature assignment of the indelible term, “venom”, implies active functional use in prey subjugation, digestion and/or self-defense and carries secondary medical as well as legal implications. Until these data are reproduced by independent investigations and further information about their function(s) is procured, it is premature and misleading to refer to them as “venoms”. For example, data that suggest hypotensive effects of V. varius oral products must be tempered with early research that showed similar potent vasopressor and/or vascular permeability effects of feline and human saliva (Gibbs, 1935; Levy and Appleton, 1942). Also, human saliva is toxic and contains multiple classes of ≥309 proteins (including toxins) that can be found in venoms (Bonilla et al., 1971; Hu et al., 2005; Weinstein et al., 2010).

In regard to the potential medical effects of these polypeptides as might be delivered in a bite from one of these lizards, there is no acceptably documented clinical information that supports any medical risk. There are two publications, one in a herpetological journal (Ballard and Antonio, 2001), and another in an obscure Russian periodical (Sopiev et al., 1987), that anecdotally describe “toxic effects” of bites from the desert monitor (Varanus griseus). However, these accounts offer only clinically unverified anecdote with unqualified descriptions of signs/symptoms that could be due to anxiety or somatosensory amplification. Therefore, to date, there are no data that support any significant medical risk aside from physical trauma (that may be serious) that can result from a bite from any of these anguimorphan or iguanian lizards. Literally thousands of iguanid and varanid lizards are kept privately in captivity, and, to date, there hasn’t been a single case of envenoming by any, but there have been a significant number of bites that featured traumatic soft tissue injury, sometimes with secondary complications such as cellulitis (see Weinstein et al., 2010 and Weinstein et al., 2011, for a discussion of some of these cases).

Thus, until there is achieved a more comprehensive scientific as well as biomedical understanding of these interesting saurian oral products, their biological roles and medical significance remain unestablished.

1 This refers to lizards other than those of the family Helodermatidae that contains two well-documented venomous species (H. suspectum and H. horridum), and several sub-species.

References

Ballard, V, Antonio, FB. 2001. Varanus griseus . Toxicity. Herpetol. Rev.32, 261.

Bonilla, CA, Fiero, MK, Seifert, W. 1971. Comparative biochemistry and pharmacology of salivary glands. 1. Electrophoretic analysis of the proteins in the secretions from human parotid and reptilian (Duvernoy's) glands. 1. Chromatogr. 56: 368-372.

Fry, BG, Vidal, N, Norman, IA, Vonk, FI, Scheib, H, Ramjan, SFR, Kuruppu, Fung, SK, Hedges, SB, Richardson, MK, Hodgson, WC, Ignjatovic, V, Summerhayes, R, Kochva, E. 2006. Early evolution of the venom system in lizards and snakes. Nature 439:584-88.

Fry, BG, Wroe, S, Teeuwisse, W, van Osch, MJ, Moreno, K, Ingle, J, McHenry, C, Ferrara, T, Clausen, P, Scheib, H, Winter, KL, Greisman, L, Roelants, K, van der Weerd, L, Clemente, CJ, Giannakis, E, Hodgson, WC, Luz, S, Martelli, P, Krishnasamy, K, Kochva, E, Kwok, HF, Scanlon, D, Karas, J, Citron, DM, Goldstein, EJ, McNaughtan, JE, Norman, JA. 2009. A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus. Proc. Natl. Acad. Sci. USA. 106: 8969-8974.

Fry, BG, Casewell, NR, Wüster, W, Vidal, N, Young, B, Jackson, NWJ. 2012. The structural and functional diversification of the Toxicofera reptile venom system. Toxicon xx: xx-xx.

Gibbs, OS. 1935. On the alleged occurrence of acetylcholine in the saliva. J. Physiol. 84: 33-40.

Hu, S, Xie, Y, Ramachandran, P, Ogorzalek, Loo, RR, Li, Y, Loo, JA and Wong, DT. 2005. Large-scale identification of proteins in human salivary proteome by liquid chromatography/mass spectrometry and two-dimensional gel electrophoresis-mass spectrometry. Proteomics 5: 1714-1728.

Levy, BM, Appleton, JLT. 1942. Effect of saliva on capillary permeability. J. Dent. Res. 21: 505-508.

Sopiev, O, Makeev, BM, Kudryavstsev, SB, Makarov, AN. 1987. A case of intoxication by a bite of the gray monitor (Varanus griseus).  Izv. Akad. Nauk Turkm. SSR. Ser. Biol. Nauk 87, 78.

Weinstein, SA, Smith, TL, Kardong, KV. 2010. Reptile venom glands: Form, function, and future. Pp. 65-91. In: CRC Handbook of Reptile Venoms and Toxins, Mackessy, SP (ed.), CRC, Taylor Francis, Boca Raton, pp. 521.

Weinstein, SA, Warrell, DA, White, J, Keyler, DE. 2011. “Venomous Bites From Non-Venomous Snakes: A Critical Analysis of Risk and Management of “Colubrid” Snake Bites”. Elsevier Science, Oxford, pp. 364.