HEPATOTOXICITY OF RATTLESNAKE (CROTALUS DURISSUS TERRIFICUS) VENOM IN RATS

¹França, R.F.; ¹Bortolin, K.; ¹Salles, R.P.; ¹Franco, A.D.; ¹Miné, C.A.C.; ¹Kuga, M. T.; ¹Lopes-Martins, R.A.B.; ¹Cogo, J.C.; ¹Prianti, A.C.; ²Carvalho, V.A.P.; ³Hyslop, S.;¹Ribeiro, W.

¹Departamento de 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 venom of the South American rattlesnake Crotalusdurissus terrrificus has neurotoxic, nephrotoxic and myotoxic activities. In this study, we examined the  hepatotoxicity of C. d. t. venom in rats. Male Wistar rats (200±20g) received 100, 200 and 300 mg of venom/kg intramuscular and were killed 3, 6, 9 and 12 h later. The hepatocellular damage was assessed by measuring the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transferase (GGT) and bilirubin. Samples of hepatic tissue were also processed for histological analysis. With the lowest dose of venom tested, liver function returned to normal range after 12 h (AST: 74,16 ± 3,36U/L; ALT: 31,43±2,84U/L; AP: 56,68±1,87U/L; GGT: 4,856 ± 0,038U/L) and liver shower low number of inflammatory cells and eosynophilic areas. Bilirrubin were not significantly different between the groups. Increasing the doses we observed progressive lesion establishment. The higher values were observed 12h after administration of 300 mg of venom (AST: 174,54±12,41U/L; ALT: 85,49±4,61U/L; AP: 76,81±8,83U/L; GGT: 6,738±0,255U/L). Histologically, were found vascular changes especially on endothelial layer and an increase of cellular damage, inflammatory cell infiltration, sinusoidal and portal congestion. C. d. terrificus venom caused dose and time-dependent hepatic damage.  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.

Financial support: FAPESP, CAPES

Correspondence to: rffranca@yahoo.com.br