Effect of purified Russell’s viper venom-factor X activator (RVV-X) on renal hemodynamics, renal functions, and coagulopathy in rats

Abstract

Acute renal failure (ARF) is the most frequent and a serious complication in victims of Russell’s viper snakebites. Russell’s viper venom-factor X activator (RVV-X) has been identified as a main procoagulant enzyme involving coagulopathy, which might be responsible for changes in renal hemodynamics and renal functions. Here, we purified RVV-X from crude Russell’s viper venom to study renal hemodynamics, renal functions, intravascular clot, and histopathological changes in Sprague–Dawley rats. Changes in renal hemodynamics and renal functions were evaluated by measuring the mean arterial pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), effective renal blood flow (ERBF), renal vascular resistance (RVR), and fractional excretion of electrolytes. After 10 min, rats receiving both crude venom and purified RVV-X decreased GFR, ERPF, and ERBF and increased RVR. These changes correlated to renal lesions. Along with the determination of intravascular clot, rats injected with purified RVV-X increased the average D-dimer level and reached a peak at 10 min, declined temporarily, and then reached another peak at 30 min. The temporal association between clots and renal dysfunction was observed in rats within 10 min after the injection of purified RVV-X. These findings suggested RVV-X as a major cause of renal failure through intravascular clotting in the renal microcirculation.

A Novel Heparin-dependent Inhibitor of Activated Protein C That Potentiates Consumptive Coagulopathy in Russell's Viper Envenomation

“…Since APC deficiency is associated with microvascular thrombosis and that DIC is always manifested with renal dysfunction (42), it is speculated that the occlusion of glomerular capillaries induced by DrKIn-I-mediated APC inhibition may be the cause of acute renal failure. Although it has been documented that RVV-induced renal failure may be due to the direct nephrotoxic components in the venom (43), other studies have shown that intravascular clotting and hemolysis may be the main cause of renal failures in these patients (44,45). In support of our hypothesis, it was found that none of the envenomed patients who did not develop DIC suffered from renal failures (46).…”

A Brief Appraisal on Russell’s Viper Venom (Daboia russelii russelii) Proteinases

“…They suggested that the changes in hemodynamics were possibly caused by the presence of some proteolytic enzymes in the RVV although the RVV proteinase(s) actually responsible for this pharmacological effect was not identified by them. Later, it was reported that RVV-X is the key component that causes renal dysfunction and coagulopathy in experimental animals (Suntravat et al 2011). Changes in renal hemodynamics and renal functions such as decreased glomerular filtration rate (GFR), effective renal plasma flow (ERPF), effective renal blood flow (ERBF), and increased renal vascular resistance (RVR) suggested the formation of renal lesions due to RVV-X treatment in experimental animals (Suntravat et al 2011).…”

“…Moreover, RV antivenom could also effectively prevent the D-dimer formation caused by purified RVV-X, under in vivo conditions when injected intravenously prior to RVV-X administration (Suntravat et al 2011). Further, no apparent histopathological changes in kidneys and lungs were observed in rats receiving RV antivenom along with purified RVV-X (Suntravat et al 2011). …”

“…RVV-X does not show esterase activity toward benzoyl-Phe-Val-Arg p-nitroanilide or benzoylarginine ethyl ester and is highly specific for factor X (Furie and Furie 1976). Neutralization study of RVV-X with commercial anti-RV antivenom revealed that the factor X activator activity of purified RVV-X toward its specific chromogenic substrate (S-2765) could be completely neutralized when taken in the ratio of 250:1 (w/w) (Suntravat et al 2011). Moreover, RV antivenom could also effectively prevent the D-dimer formation caused by purified RVV-X, under in vivo conditions when injected intravenously prior to RVV-X administration (Suntravat et al 2011).…”

“…Neutralization study of RVV-X with commercial anti-RV antivenom revealed that the factor X activator activity of purified RVV-X toward its specific chromogenic substrate (S-2765) could be completely neutralized when taken in the ratio of 250:1 (w/w) (Suntravat et al 2011). Moreover, RV antivenom could also effectively prevent the D-dimer formation caused by purified RVV-X, under in vivo conditions when injected intravenously prior to RVV-X administration (Suntravat et al 2011). Further, no apparent histopathological changes in kidneys and lungs were observed in rats receiving RV antivenom along with purified RVV-X (Suntravat et al 2011).…”