Bothrops atrox is responsible for most accidents involving snakes in the Brazilian Amazon and its venom induces serious systemic and local effects. The local effects are not neutralized effectively by commercial antivenoms, resulting in serious sequelae in individuals bitten by this species. This study investigates the local inflammatory events induced in mice by B. atrox venom (BaV), such as vascular permeability, leukocyte influx and the release of important inflammatory mediators such as cytokines, eicosanoids and the chemokine CCL-2, at the injection site. The effect of BaV on cyclooxygenase (COX-1 and COX-2) expression was also investigated. The results showed that intraperitoneal (i.p.) injection of BaV promoted a rapid and significant increase in vascular permeability, which reached a peak 1 h after venom administration. Furthermore, BaV caused leukocyte infiltration into the peritoneal cavity between 1 and 8 h after i.p. injection, with mononuclear leukocytes (MNs) predominating in the first 4 h, and polymorphonuclear leukocytes (PMNs) in the last 4 h. Increased protein expression of COX-2, but not of COX-1, was detected in leukocytes recruited in the first and fourth hours after injection of BaV. The venom caused the release of eicosanoids PGD 2, PGE 2, TXA 2 and LTB 4, cytokines TNF-α, IL-6, IL-10 and IL-12p70, but not IFN-γ, and chemokine CCL-2 at different times. The results show that BaV is able to induce an early increase in vascular permeability and a leukocyte influx to the injection site consisting mainly of MNs initially and PMNs during the later stages. These phenomena are associated with the production of cytokines, the chemokine CCL-2 and eicosanoids derived from COX-1 and COX-2.
Bibliographical noteFunding Information:
The authors thank to Renata Hage Amaral for technical assistance. This investigation was supported by research grants from FAPESP , Brazil (grants 07/03336-9 , 09/50896 and 10/51150-4 ). C.T. is recipient of CNPq-PQ (grant 306099/2008-0 ); V.M. is recipient of Pos doctoral fellowship from FAPESP-Brazil (grant 07/03337-5 ); M.C.S. is recipient of CNPq-PQ (grant 302615/2010-5 ); N.G.N. is recipient of PhD fellowship from CAPES, H.B.S. is recipient of PhD fellowship from FAPESP (grants 09/08559-1 ) and M.R.D.L. is recipient of CNPq-PQ (grant 302476/2010-5 ).
- Bothrops atrox