Carbon monoxide attenuates the effects of snake venoms containing metalloproteinases with fibrinogenase or thrombin-like activity on plasmatic coagulation

Abstract

Exposure of plasma to iron and carbon monoxide (CO) renders fibrinogen resistant to fibrinogenolytic or thrombin-like activity contained in pit viper venom. However, the direct effects of iron/CO on venom activity are unknown. Thus, we assessed if four different, metalloproteinase containing snake venoms exposed to iron/CO or CO alone could attenuate their fibrinogenolytic or thrombin-like activity. Venom (0-500 mu g ml(-1)) was exposed to 0-10 mu M FeCl3 and/or 0-100 mu M carbon monoxide releasing molecule-2 (CORM-2), or inactivated CORM-2 (iCORM-2) for 3 min at room temperature. Venom solution (0-8 mu g ml(-1) final concentration) was then placed in citrated human plasma containing tissue factor, followed by CaCl2 addition for commencement of coagulation. Data were determined with thrombelastography for 10-15 min at 37 degrees C. Iron had no effect on the first venom tested, so only CO was investigated subsequently. Exposure of venom to CO attenuated fibrinogenolytic or thrombin-like activity, and iCORM-2 did not affect the venom activities. Further investigation of the effect of CO exposure on similar venoms is justified.