Pharmacological characterization of the rat paw edema induced by Bothrops lanceolatus (Fer de lance) venom

The inflammatory response induced by Bothrops lanceolatus venom (BLV) in th e rat hind-paw was studied measuring paw edema. Non-heated BLV (75 mug/paw) caused a marked paw edema accompanied by intense haemorrhage whereas heate d venom (97 degreesC, 30 s; 12.5-100 mug/paw) produced a dose- and time-dep endent non-haemorrhage edema. The response with heated BLV was maximal with in 15 min disappearing over 24 h. Heated venom was then routinely used at t he dose of 75 mug/paw. The prostacyclin analogue iloprost (0.1 mug/paw) pot entiated by 125% the venom-induced edema. The histamine H-1 receptor antago nist mepyramine (6 mg/kg) or the serotonin/histamine receptor antagonist cy proheptadine (6 mg/kg) partially inhibited BLV-induced edema whereas the co mbination of both compounds virtually abolished the edema. The lipoxygenase inhibitor BWA4C (10 mg/kg), but not the cyclooxygenase inhibitor indometha cin (10 mg/kg), significantly inhibited the edema (35% reduction; P < 0.05) . Dexamethasone (1 mg/kg) also markedly (P < 0.001) reduced venom-induced e dema. The brady-kinin B-2 receptor antagonist Hoe 140 (0.6 mg/kg) reduced b y 30% (P < 0.05) the venom induced edema, whereas the angiotensin-convertin g enzyme inhibitor captopril (300 <mu>g/paw) potentiated by 42% (P < 0.05) the edema. Bothrops lanceolatus antivenon (anti-BLV) reduced by 28% (P < 0. 05) the venom-induced edema while intravenous administration of antivenom f ailed to affect the edema. In conclusion, BLV-induced rat paw edema involve s mast cell degranulation causing local release of histamine and serotonin, a phenomenon mediated mainly by kinins and lipoxygenase metabolites. Addit ionally, the use of a specific Bothrops lanceolatus antivenom, given subpla ntarily or intravenously, revealed to be little effective to prevent BLV-in duced edema. (C) 2001 Elsevier Science Ltd. All rights reserved.