title: Pharmacological characterization of the rat paw edema induced by Bothrops lanceolatus (Fer de lance) venom.
abstract: The inflammatory response induced by Bothrops lanceolatus venom (BLV) in the rat hind-paw was studied measuring paw edema. Non-heated BLV (75microg/paw) caused a marked paw edema accompanied by intense haemorrhage whereas heated venom (97 degrees C, 30s; 12.5-100microg/paw) produced a dose- and time-dependent non-haemorrhagic edema. The response with heated BLV was maximal within 15min disappearing over 24h. Heated venom was then routinely used at the dose of 75microg/paw. The prostacyclin analogue iloprost (0.1microg/paw) potentiated by 125% the venom-induced edema. The histamine H(1) receptor antagonist mepyramine (6mg/kg) or the serotonin/histamine receptor antagonist cyproheptadine (6mg/kg) partially inhibited BLV-induced edema whereas the combination of both compounds virtually abolished the edema. The lipoxygenase inhibitor BWA4C (10mg/kg), but not the cyclooxygenase inhibitor indomethacin (10mg/kg), significantly inhibited the edema (35% reduction; P<0.05). Dexamethasone (1mg/kg) also markedly (P<0.001) reduced venom-induced edema. The bradykinin B(2) receptor antagonist Hoe 140 (0.6mg/kg) reduced by 30% (P<0.05) the venom induced edema, whereas the angiotensin-converting enzyme inhibitor captopril (300microg/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 failed to affect the edema. In conclusion, BLV-induced rat paw edema involves mast cell degranulation causing local release of histamine and serotonin, a phenomenon mediated mainly by kinins and lipoxygenase metabolites. Additionally, the use of a specific Bothrops lanceolatus antivenom, given subplantarily or intravenously, revealed to be little effective to prevent BLV-induced edema.
authors.affiliation: Departamento de Farmacologia, FCM, UNICAMP, CP 6111, 13081-970, Campinas, SP, Brazil.
authors.lastname: de Faria L
authors.forename: E
authors.initials: E
authors.lastname: Antunes
authors.forename: C
authors.initials: C
authors.lastname: Bon
authors.forename: A L
authors.initials: AL
authors.lastname: de Araújo
mesh_terms: D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced*; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D003435:Crotalid Venoms; D014665:Vasodilator Agents; D016285:Iloprost