Received: April 29, 2008

Accepted: September 16, 2008

Abstract published online: October 13, 2008

Full paper published online: February 28, 2009

ACUTE HEPATOTOXICITY OF Crotalus durissus terrificus (SOUTH AMERICAN RATTLESNAKE) VENOM IN RATS

França RF (1), Vieira RP (2), Ferrari EF (1), Souza RA (1), Osorio RAL (1), Prianti-Jr. ACG (1), Hyslop S (3), Zamuner SR (1), Cogo JC (1), Ribeiro W (1)

(1) Laboratory of Physiology and Pharmacodynamic, Institute of Research and Development, Vale do Paraíba University, UNIVAP, São José dos Campos, São Paulo State, Brazil; (2) Department of Pathology and Physical Therapy, School of Medicine, University of São Paulo, USP, São Paulo, São Paulo State, Brazil; (3) Department of Pharmacology, School of Medical Sciences, State University of Campinas, UNICAMP, Campinas, São Paulo State, Brazil.

ABSTRACT: Venom of the South American rattlesnake, Crotalus durissus terrificus (Cdt), presents myotoxic and neurotoxic outcomes, but reports on its effects on the liver are scarce. This study examined the hepatotoxicity resulting from Cdt venom administration (100, 200 and 300 g/kg) in male Wistar rats. Animals were studies at 3, 6, 9 and 12 hours after venom injection. The hepatotoxicity was assessed through serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), bilirrubin and also by histopathological evaluation. All the different concentrations of Cdt venom resulted in increased levels of hepatic enzymes, when compared with the control group, except for the 100 g/kg dose, which presented normal levels at 9 and 12 hours after venom administration. Bilirrubin levels remained unchanged by Cdt venom. Histological analysis revealed endothelial damage, inflammatory cell infiltration, as well as sinusoidal and portal congestion. Based on these observations, we may conclude that Cdt venom causes dose- and time-dependent hepatic damage in rats, characterized by elevated hepatic enzyme levels and histological alterations.

KEY WORDS: Crotalus durissus terrificus, hepatotoxicity, histology, AST, ALT, rattlesnake, liver enzymes, venom.

CONFLICTS OF INTEREST: There is no conflict.

FINANCIAL SOURCE: FAPESP and FVE/UNIVAP.

CORRESPONDENCE TO:

WELLINGTON RIBEIRO, Laboratório de Fisiologia e Farmacodinâmica, Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, UNIVAP, Av. Shishima Hifumi, 2911, São José dos Campos, SP, 12.244-000, Brazil. Phone: +55 12 3947 1106. Email: gton@univap.br.