In vitro nephrotoxicity of Russell's viper venom

In vitro nephrotoxicity of Russell's viper venom. To assess direct nephrotoxicity of Russell's viper venom (RVV; Daboia russelii siamensis ), isolated rat kidneys were perfused in single pass for 120min. Ten μg/ml and 100 µg/ml RVV were administered 60 minutes and 80 minutes, respectively, after starting the perfusion. Furthermore, cultured mesangial cells and renal epithelial LLC-PK 1 and MDCK cells were exposed to RVV (100 to 1000 µg/ml) for 5 minutes up to 48 hours. The IPRK dose-dependently exhibited reductions of renal perfusate flow (RPF, 7.7 ± 2.4 vs. 16.5 ± 0.7ml/min g kidney wt in controls, experimental values given are those determined 10 minutes after termination of 100 µg/ml RVV admixture), glomerular filtration rate (GFR 141 ± 23 vs. 626 ± 72 µg/min g kidney wt) and absolute reabsorption of sodium (T Na 8 ± 1.7 vs. 79 ± 9 µmol/min g kidney wt), and an increased fractional excretion of sodium (FE na 60 ± 7 vs. 8 ± 0.8%) and water (FE H 2 O 68 ± 3.2 vs. 13 ± 1.2%). Urinary flow rate (UFR) showed both oliguric and polyuric phases. Functional alterations of this type are consistent with ARF. Light and electron microscopy of perfusion fixed IPRK revealed an extensive destruction of the glomerular filter and lysis of vascular walls. Various degrees of epithelial injury occurred in all tubular segments. In cell culture studies RVV induced a complete disintegration of confluent mesangial cell layers, beginning at concentrations of 200 µg/ml. In epithelial LLC-PK 1 and MDCK cell cultures only extremely high doses of RVV (>600 and 800 µg/ml, respectively) led to microscopically discernible damage. These results clearly demonstrate a direct dose dependent toxic effect of RVV on the IPRK, directed primarily against glomerular and vascular structures, and on cultured mesangial cells.