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.

A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages

“…To our knowledge, this is the first demonstration that LDs induced by a group IIA sPLA 2 are equipped with a COX-1 enzymatic system and are involved in synthesis of a lipid mediator implicated in inflammatory resolution, such as 15-d-PGJ 2 . In addition, it should be noted that release of the anti-inflammatory mediator 15-d-PGJ 2 is in line with the immunomodulatory effects of CB and sheds new light on the mechanisms by which whole Crotalus snake venom and CB, its major sPLA 2 , can reduce or abolish inflammatory events 5, 68 .…”

Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice

“…It was also shown that LXA 4 was involved in the inhibitory effect of CTX on the phagocytic activity of macrophages in vitro [ 49 ]. Furthermore, LXA 4 induced by CTX can be correlated with the inhibition of neutrophil migration to the peritoneal cavity induced by carrageenan injection or paw edema in mice injected with Bacillus Calmette-Guérin (BCG) [ 50 , 97 ]. In accordance with these reports, our data suggest that CTX induces an anti-inflammatory status in mice able to control the intestinal inflammation induced by the TNBS.…”

Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4

“…The antitumoral effects of CTX have also been reported in patients with lung and mammary carcinoma [ 8 ]. Evidence has been accumulated that CTX presents inhibitory effects on inflammatory response [ 13 , 14 ]. Inflammation is closely associated with cancer growth [ 15 ].…”