Myotoxicity induced by Cerastes cerastes venom: Beneficial effect of heparin in skeletal muscle tissue regeneration

Myonecrosis is a relevant tissue damage induced by snakes of Viperidae family often leading to permanent tissue and function loss and even amputation. The aim of this study was to evaluate the effect of heparin on skeletal muscle tissue regeneration after Cerastes cerastes envenomation. Mice received either the venom (1 LD50) by i.m. route, or the venom followed, by heparin administration by i.v. route at 15 min and 4 h. Obtained results showed that Cerastes cerastes venom induced deep tissue structure alterations, characterized mainly by edema, hemorrhage, myonecrosis and inflammation. Myotoxicity was correlated with increased CK levels in sera, concomitant with their decrease in muscle tissue homogenates. Muscle wet weight was restored within 2 weeks after heparin treatment and 28 days in the envenomed group. Heparin treatment significantly decreased MPO activity, suggesting an anti-inflammatory effect. NO, HGF, VEGF and G-CSF levels were increased after heparin administration. These mitogenic factors constitute potent stimuli for satellite and endothelial cells improving, thus, muscle regeneration. This study showed that muscle tissue recovery was significantly enhanced after heparin treatment. Heparin use seems to be a promising therapeutic approach after viper envenomation.