EFFECTS OF Bothrops asper (BaV) AND Bothrops jararaca (BjV) VENOMS ON THE RELEASE OF PROSTANOIDS AND EXPRESSION OF CYCLOOXYGENASES

Zamuner, S.R.(1), Wallace, J.L.(2), Olivo, R.A.(1), Teixeira, C.F.P.(1)

(1)Laboratório de Farmacologia, Instituto Butantan, São Paulo, Brasil, (2)Dept of Pharmacology and Therapeutics, University of Calgary, Canada.

Venoms from snakes of genus Bothrops cause pronounced local effects in the victims, which are characterized by necrosis, hemorrhage and edema. Previous results of our laboratory have showed that BaV- and BjV-induced paw edema is markedly reduced by indomethacin pre treatment. In the present work, the effects of the BaV and BjV on the release of prostanoids(PGE₂ and PGD₂) and expression of COX-1 and COX-2 were investigated. Groups of male mice were injected i.p. with BaV or BjV (250 mg/kg) or saline. Peritoneal washes were collected and centrifuged at selected periods of time and concentrations of PGE₂ and PGD₂ were determined by specific enzymatic immunoassay in the supernatant. Expression of COX-1 and COX-2 was evaluated by western blot analyses in leukocytes. BaV and BjV induced a significant release of PGE₂. BaV but not BjV induced the release of PGD_2. Both venoms increased the expression of COX-2, BaV from 3 to 12 hours and BjV at only 12 hours. Expression of COX-1 was not affect by both venoms. These results indicate that BaV and BjV induce local production of prostanoids in the site of their injection. This effect is correlated with expression of COX-2, but not COX-1. Absence of PGD₂ modulation on the release of PGE₂ was observed in our experimental model. Since the effect of BaV on the expression of COX-2 was seen earlier than that of BjV, the components responsible for these effects may differ for both venoms.

Financial support: FAPESP

CORRESPONDENCE TO:

Stella Regina Zamuner, Rua Mario Prunes, 55 Apto. 21C, Campinas, SP, CEP: 13055-221, Brasil, Email: zamuner@usp.br