IN-VITRO NEPHROTOXICITY OF RUSSELLS VIPER VENOM

To assess direct nephrotoxicity of Russell's viper Venom (RVV; Daboia russelii siamensis), isolated rat kidneys were perfused in single pass for 120 min. Ten mu g/ml and 100 mu g/ml RVV were administered 60 min utes and 80 minutes, respectively, after starting the perfusion. Furth ermore, cultured mesangial cells and renal epithelial LLC-PK1 and MDCK cells were exposed to RVV (100 to 1000 mu g/ml) for 5 minutes up to 4 8 hours. The IPRK dose-dependently exhibited reductions of renal perfu sate flow (RPF, 7.7 +/- 2.4 vs. 16.5 +/- 0.7 ml/min g kidney wt in con trols, experimental values given are those determined 10 minutes after termination of 100 mu g/ml RVV admixture), glomerular filtration rate (GFR 141 +/- 23 vs. 626 +/- 72 mu l/min g kidney wt) and absolute rea bsorption of sodium (T-Na 8 +/- 1.7 vs. 79 +/- 9 mu mol/min g kidney w t), and an increased fractional excretion of sodium (FE(Na) 60 +/- 7 v s. 8 +/- 0.8%) and water (FE(H2O) 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 m icroscopy of perfusion fixed IPRK revealed an extensive destruction of the glomerular filter and lysis of vascular walls. Various degrees of epithelial injury occurred in ail tubular segments. In cell culture s tudies RVV induced a complete disintegration of confluent mesangial ce ll layers, beginning at concentrations of 200 mu g/ml. In epithelial L LC-PK1 and MDCK cell cultures only extremely high doses of RVV (>600 a nd 800 mu g/ml, respectively) led to microscopically discernible damag e. These results clearly demonstrate a direct dose dependent toxic eff ect of RVV on the IPRK, directed primarily against glomerular and vasc ular structures, and on cultured mesangial cells.