Inhibitory effect of Crotalus durissus terrificus venom on chronic edema induced by injection of bacillus Calmette-Guérin into the footpad of mice

Abstract

In this study, we evaluated the effect of the Crotalus durissus terrificus (Cdt) venom on the chronic paw edema induced by the injection of bacillus Calmette-Guérin (BCG) into the footpad of mice. The BCG injection evoked chronic edema, which was significantly diminished in animals treated subcutaneously (s.c.) with Cdt venom 1 h before or after the BCG injection. This inhibition persisted throughout the evaluation period (15 days). In mice injected with Cdt venom 6 or 11 days after injection of BCG, we observed a significant reduction in edema only in the period after the venom injection. While studying possible mechanisms involved in this inhibition, we observed that pre-treatment with dexamethasone, zileuton or Boc2 (a selective antagonist of formyl peptide receptors), but not with indomethacin, canceled out the inhibitory effect of Cdt venom on the edema induced by BCG. These results strongly suggest that this rattlesnake venom can stimulate the generation of mediators from the lipoxygenase pathway, which can down-regulate this chronic inflammatory edema. Using fractionated venom, the results indicated that crotoxin was the only component of Cdt venom responsible for this inhibitory effect. These results indicated that crotoxin, the main toxin of the C. durissus terrificus venom, has a significant inhibitory effect on BCG-induced chronic edema, possibly by generating anti-inflammatory mediators from the lipoxygenase pathway.