Enzymatic and antileishmanial activities of five rear-fanged snake venoms

MARÍA ELISA PEICHOTO; FLAVIO LUIZ TAVARES; GREGORY DEKREY; STEPHEN P. MACKESSY

Barcelona (España)

Congreso; XII International Congress of Toxicology; 2010

International Union of Toxicology

Relatively few studies have investigated the composition and biological activities of the venoms of rear-fanged snakes. In this study, we conducted a comparative analysis of the protein composition and enzymatic properties of the venoms of the South American rear-fanged snakes Philodryas baroni (PbV), Philodryas olfersii olfersii (PooV) and Philodryas patagoniensis (PpV), and the North American rear-fanged snakes Hypsiglena torquata texana (HttV) and Trimorphodon biscutatus lambda (TblV). Sodium dodecyl sulfate-polyacrylamide electrophoresis showed distinct protein patterns among the venoms, with masses ranging from ~6 kDa to 95 kDa. All five venoms degraded azocasein, and in all cases this activity was significantly inhibited by 5 mM EDTA. PooV exhibited the highest level of thrombin-like activity when tested on both substrates tosyl-Gly-Pro-ArgpNA and Bz-Phe-Val-ArgpNA. The five venoms were able to hydrolyze acetylthiocoline, but PpV and TblV exhibited the highest level of acetylcholinesterase activity. Only TblV showed phospholipase A2 activity. We also tested the antiparasitic activity of the five venoms studied against Leishmania major, the causative agent of cutaneous leishmaniasis. TblV showed antileishmanial activity (IC50 of 108.6 ìg/mL). PpV also significantly decreased parasitic growth (p < 0.05), but a final concentration of 1.7 mg/mL was necessary to inhibit proliferation by 51.5%. PbV, PooV and HttV, at final concentration of 562, 524 and 438 ìg/mL respectively, had no significant effect on L. major growth. This is the first report of rear-fanged snake venoms with antileishmanial activity, and these results open new possibilities to finding protein-based drugs that might be used as possible agents against leishmaniasis. In addition, we discuss implications of our findings for the evolution of venoms among New World rear-fanged snakes.