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Involvement of lipidic mediators in the edema formation induced by Bothrops fonsecai venom

Ludmila Guimarães-Souza, Vera Lucia S. Rigoni, Ana Maria Barbosa, José Carlos Cogo, Stella Regina Zamuner

Med Sci Tech 2012; 53(4): RA181-185

ID: 883655

Available online:

Published: 2012-12-17


#883655

Background:    Edema and pain are the most pronounced local effects caused by Bothrops snake venom. These local effects are not neutralized by antivenom therapy. The present work was designed to examine the ability of B. fonsecai venom to cause edema in the mouse hind paw, and investigated some of the mediators involved in this response. The efficacy of commercial antivenom in neutralizing the edema formation induced by B. fonsecai was also evaluated.
    Material/Methods:    A total of 35 male Swiss mice were used for the study. The edematogenic effect was evaluated by plethysmograph at various time points: 15 min, 30 min, 1 h, 3 h, 6 h, and 24 h after the injection of 0.5, 1, and 5 µg/paw of B. fonsecai venom or saline (control). The animals were treated with: dexamethasone, an inhibitor of PLA2 activity, 1 mg/kg, IP, 1 h before venom; meloxicam, a selective inhibitor of COX-2, 3 mg/kg, IP, administered 1 h before venom; L-NAME, a non-specific inhibitor of nitric oxide synthase, 1 h before venom; and a volume of 60 µl of antivenom was injected intravenously immediately after intraplantar injection of B. fonsecai venom.
    Results:    Our results showed that B. fonsecai venom caused a dose-dependent edema. The dose of 1 µg/paw was the best dose that caused edema without macroscopic hemorrhage. The peak of edema was observed at 1 h after venom injection. Pretreating the mice with dexamethasone and meloxicam significantly attenuated venom-induced edema, whereas LNAME had no effect. The administration of antivenom immediately after venom injection also significantly inhibited venom-induced edema at 6 h.
    Conclusions:    These results show that B. fonsecai venom causes edema in the mouse hind paw and that this response is mediated, at least in part, by arachidonic acid metabolites formed by cyclooxygenases. The neutralization by commercial antivenom indicates that the venom components responsible for edema are recognized by the antivenom and share immunological identity with other Bothrops species.

Keywords: oedema, antivenom, cyclooxygenase, bothrops fonsecai, Nitric Oxide



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