Poster 091 - Effect of single administration of diltiazem on liver injury induced by crotalid

Poster 91. Congresso da Sociedade Brasileira de Toxinologia, 8., Symposium of the Pan American Section of the International Society on Toxinology, 8., 2004, Angra dos Reis, Brasil. Abstracts... J. Venom. Anim. Toxins incl.Trop. Dis., 2004, 10, 3, p.450.

EFFECT OF SINGLE ADMINISTRATION OF DILTIAZEM ON LIVER INJURY INDUCED BY CROTALID VENOM

¹França, R.F.; ¹Bortolin, K.; ¹Vieira, R. P.; ¹Salles, R. P., ¹Franco, A. D., ¹Miné, C. A. C.; ¹Lopes-Martins, R. A. B.; ¹Cogo, J. C.; ¹Prianti, A.C.; ²Brandão, A.A.H.; ³Hyslop, S.; ¹Ribeiro, W.

¹Depto. Fisiologia e Farmacodinâmica, IP&D, UNIVAP, São Paulo, Brasil. ²Departamento de Farmacologia, UNESP, São Paulo, Brasil. ³Lab. Farmacologia e Bioquímica, UNICAMP, São Paulo, Brasil.

The action of ophidian venom on liver has been investigated, although the mechanism are not understood. Hepatic alterations were observed on victims of Crotalusdurrissus terrificus bite. Several mechanisms by which hepatotoxic agents kill cells can be operable at same time with a single toxicant; one of these mechanisms is related to intracellular calcium homeostasis disruption. Since calcium may involved on hepatocellular damage caused by crotalid venom, calcium channel blockers could exert an influence on venom-induced hepatotoxicity. This study examined the effect of single administration of calcium channel blocker diltiazem (30mg/kg i.p.) on liver injury induced by crotalid venom (200µg/kg i.m.) on male rats Wistar (200±20g). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) were measured to evaluate the hepatic condition, as well the histological features of hepatic tissue were analysed. At the dose used, diltiazem was unable to protect the liver from alterations verified after venom administration. The opposite was observed, according to the high values of AST and ALT activities ( after 3 h: AST 124,67±9,28U/L; ALT 59,19±7,29U/L; after 12h: AST 165,28±11,60U/L; ALT 72,79±63,7U/L ). These data were significantly different from control group ( AST: 78,36±4,39U/L; ALT: 24,09±3,35U/L ). Cellular changes were observed histologically, such as expressive periportal inflammatory infiltration, increased of Kupffer cells, hepatocyte degeneration and vascular congestion. The pharmacological knowledge of ophidian venom may contribute to understand the pathological process that occur in consequence of envenoming. Data were present as mean±SEM and were analysed by one-way of variance (ANOVA). The Student’s “t”test was performed for statistical evaluations between the groups (n=7). Significance level was considered for p<0.05.