Avaliação da toxicidade sistêmica aguda induzida pelo veneno de Micrurus corallinus (cobra coral) em ratos tratados com varespladib associado ao soro anti-elapídico

Abstract

The present study investigated the action of varespladib (VPL) alone or in combination with a coral snake antivenom (CAV) on the local and systemic effects induced by Micrurus corallinus venom in rats. Adult male Wistar rats were exposed to venom (1.5 mg/kg – i.m.) and immediately treated with CAV (antivenom:venom ratio 1:1.5 ‘v/w’ – i.p.), VPL (0.5 mg/kg – i.p.), or both of these treatments. The animals were monitored for 120 min and then subjected to euthanasia to collect blood and tissue samples for haematological, biochemical and histopathological analysis. Venom caused local oedema without subcutaneous haemorrhage or apparent necrosis formation, with accentuated muscle morphological damage; none of the treatments prevented oedema formation, whereas CAV + VPL reduced the myonecrosis. Venom caused neuromuscular paralysis and respiratory impairment in approximately 60 min, with CAV alone failing to prevent these effects, whereas VPL and VPL + CAV prevented the neurotoxic symptoms developing. Venom increased the serum CK and AST release, which was partially prevented by CAV + VPL. The increase of LDH and ALP (hepatotoxicity) by venom were not prevented by CAV and VPL, although their combination avoided the ALP release. The increase in serum creatinine concentration (nephrotoxicity) caused by venom was prevented by all the treatments. VPL or VPL + CAV prevented the venom-induced lymphocytosis. In conclusion, VPL acts preventing the neurotoxic, nephrotoxic and inflammatory effects by M. corallinus venom and exhibits synergic action with antivenom.