Pharmacological and histopathological characterization of Bothrops lanceolatus (Fer de lance) venom-induced edema.
OBJECTIVE
Bothrops venoms cause local edema, pain, hemorrhage and necrosis. In this study, we investigated the ability of Bothrops lanceolatus venom to cause edema in rat hind paws and examined the mediators involved.


METHODS
Hind paw edema was induced in male Wister rats by the subplantar injection of venom (12.5-100 microg/paw) in the absence and presence of antagonists. Edema was quantified by hydroplethysmometry at 0.25, 0.5, 2, 4, 6 and 24 h post-injection and was expressed as the percentage increase relative to the contralateral (control) paw. The ability of the venom to release histamine from rat peritoneal mast cells was also assessed.


RESULTS
Venom caused dose- and time-dependent edema that was maximal within 15 min but disappeared after 24 h and was accompanied by hemorrhage. Dexamethasone (1 mg/kg, s.c.), methysergide (6 mg/kg, i.p.), HOE 140 (0.6 mg/kg, i.v.) and mepyramine (6 mg/kg, i.p.) significantly ( p < 0.05) reduced edema formation, whereas indomethacin (10 mg/kg, i.p.) was ineffective. Dialysis did not affect venom-induced edema. Venom (1, 10 and 30 microg/ml) caused a concentration-dependent release of histamine (13 +/- 1%, 61.9 +/- 4.6% and 73.6 +/- 2.4%, respectively; n = 5) from rat peritoneal mast cells in vitro. Histological analysis confirmed the presence of edema, hemorrhage and neutrophil infiltration. Pretreating the venom with EDTA partially inhibited the edema and hemorrhage, but did not affect the migration of neutrophils.


CONCLUSIONS
B. lanceolatus venom produced dose- and time-dependent edema in rat paws. This edema was not dependent on low molecular weight substances in the venom, but was partially dependent on a hemorrhagin and also involved the release of arachidonic acid metabolites, bradykinin, histamine and serotonin.
Guimarães
A Q
AQ
Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), 13083-970, Campinas, SP, Brasil. albetiza@fcm.unicamp.br
Cruz-Höfling
M A
MA
Ferreira de Araújo
P M
PM
Bon
C
C
Lôbo de Araújo
A
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D017837:Bothrops; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D003435:Crotalid Venoms / Q000633:toxicity*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced* / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D005121:Extremities; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism; D008784:Methysergide / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000932:Antiemetics; D002317:Cardiovascular Agents; D003435:Crotalid Venoms; D006634:Histamine H1 Antagonists; D014662:Vasoconstrictor Agents; D016718:Arachidonic Acid; D012701:Serotonin; C065679:icatibant; D003907:Dexamethasone; D006632:Histamine; D004492:Edetic Acid; D011738:Pyrilamine; D001920:Bradykinin; D007213:Indomethacin; D008784:Methysergide