Bothrops lanceolatus (Fer de lance) venom induces oedema formation and increases vascular permeability in the mouse hind paw.
The ability of snake venoms to increase vascular permeability and to induce oedema through the release of pharmacologically active substances is well known. We have studied the oedema and vascular permeability induced by Bothrops lanceolatus venom in male Swiss white mice. Paw oedema was induced by the subplantar injection of B. lanceolatus venom (125-1000 ng/paw) and was quantified as the increase in paw weight. Changes in vascular permeability were assessed by measuring the amount of Evans blue dye extravasation. The oedema and the increase in vascular permeability were maximal within 2 h and had resolved after 24 h. The administration of the vasodilator iloprost (20 ng/paw) immediately after B. lanceolatus venom potentiated the oedema and the increase in vascular permeability by approximately four-fold. Pretreating the mice with indomethacin, dexamethasone, NDGA or BW A4C inhibited the venom-induced oedema and the increase in vascular permeability. In contrast, histamine, serotonin and PAF-acether antagonists (mepyramine, cyproheptadine and WEB 2086, respectively) were ineffective. Histological examination showed that B. lanceolatus venom (250 ng and 500 ng/paw) caused thickening of the inner dermal layers which was accompanied by extensive intercellular spaces indicative of oedema. In addition, there was a marked infiltration of inflammatory cells, particularly neutrophils, into the underlying muscle layer. The latter, however, remained morphologically unaffected during the 3 h of observation. Venom doses larger than 500 ng/paw produced intense haemorrhage. These results indicate that B. lanceolatus venom induces oedema and increases vascular permeability in the mouse hind paw. The principal mediators of this inflammatory response are cyclooxygenase and lipoxygenase products.
de Araújo
A L
AL
Departamento de Farmacologia, Faculdade de Ciências Médices, Universidade Estadual de Campinas, SP, Brazil.
de Souza
A O
AO
da Cruz-Höfling
M A
MA
Flores
C A
CA
Bon
C
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology; D002199:Capillary Permeability; D003435:Crotalid Venoms / Q000633:toxicity*; D004487:Edema / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D014230:Triazoles / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001381:Azepines; D003435:Crotalid Venoms; D014230:Triazoles; C052518:WEB 2086; D016718:Arachidonic Acid