In this study, we 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 anesthetized to collect blood samples used for haematological and serum biochemical analysis; after
euthanasia, skeletal muscle, renal and hepatic tissue samples were collected for histopathological analysis. M. corallinus
venom caused local oedema without subcutaneous haemorrhage or apparent
necrosis formation, although there was accentuated muscle morphological damage; none of the treatments prevented oedema formation but the combination of CAV and VPL reduced
venom-induced myonecrosis.
Venom caused neuromuscular
paralysis and respiratory impairment in approximately 60 min following envenomation; CAV alone did not prevent the neurotoxic action, whereas VPL alone prevented neurotoxic symptoms developing as did the combination of CAV and VPL.
Venom induced significant increase of serum CK and AST release, mostly due to local and systemic
myotoxicity, which was partially prevented by the combination of CAV and VPL. The release of hepatotoxic serum
biomarkers (LDH and ALP) induced by M. corallinus
venom was not prevented by CAV and VPL when individually administered; their combination effectively prevented ALP release. The
venom-induced nephrotoxicity (increase in serum
creatinine concentration) was prevented by all the treatments. VPL alone or in combination with CAV significantly prevented the
venom-induced
lymphocytosis. In conclusion, VPL shows to be effective at preventing the neurotoxic, nephrotoxic, and inflammatory activities of M. corallinus
venom. In addition, VPL acts synergistically with
antivenom to prevent a number of systemic effects caused by M. corallinus
venom.