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

• Published in: Toxicon (Oxford) Vol. 39; no. 6; pp. 825 - 830
• Main Authors: de Faria, L, Antunes, E, Bon, C, Lôbo de Araújo, A
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-06-2001; Elsevier Science
• Subjects: Animal poisons toxicology. Antivenoms; Animals; Antivenom; Biological and medical sciences; Bothrops; Bothrops lanceolatus; Crotalid Venoms - toxicity; Edema - chemically induced; Iloprost - pharmacology; Male; Medical sciences; Rat paw edema; Rats; Rats, Wistar; Toxicology; Vasodilator Agents - pharmacology; Antivenom; Rat paw edema; Bothrops lanceolatus; Edema; Rat; Serotonin; Toxicity; Rodentia; Kinin; Inflammation; Hemorrhage; Ophidia; Histamine; Leg(animal); Vertebrata; Mammalia; Animal; Bradykinin; Venom; Reptilia; Mast cell; Mechanism of action; ACE inhibitor
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/S0041-0101(00)00213-0

The inflammatory response induced by
Bothrops lanceolatus venom (BLV) in the rat hind-paw was studied measuring paw edema. Non-heated BLV (75
μg/paw) caused a marked paw edema accompanied by intense haemorrhage whereas heated venom (97°C, 30
s; 12.5–100
μg/paw) produced a dose- and time-dependent non-haemorrhagic edema. The response with heated BLV was maximal within 15
min disappearing over 24
h. Heated venom was then routinely used at the dose of 75
μg/paw. The prostacyclin analogue iloprost (0.1
μg/paw) potentiated by 125% the venom-induced edema. The histamine H
1 receptor antagonist mepyramine (6
mg/kg) or the serotonin/histamine receptor antagonist cyproheptadine (6
mg/kg) partially inhibited BLV-induced edema whereas the combination of both compounds virtually abolished the edema. The lipoxygenase inhibitor BWA4C (10
mg/kg), but not the cyclooxygenase inhibitor indomethacin (10
mg/kg), significantly inhibited the edema (35% reduction;
P<0.05). Dexamethasone (1
mg/kg) also markedly (
P<0.001) reduced venom-induced edema. The bradykinin B
2 receptor antagonist Hoe 140 (0.6
mg/kg) reduced by 30% (
P<0.05) the venom induced edema, whereas the angiotensin-converting enzyme inhibitor captopril (300
μg/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.