In vitro nephrotoxicity of Russell's viper venom

Abstract

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 micrograms/ml and 100 micrograms/ml RVV were administered 60 minutes and 80 minutes, respectively, after starting the perfusion. Furthermore, cultured mesangial cells and renal epithelial LLC-PK1 and MDCK cells were exposed to RVV (100 to 1000 micrograms/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 +/- 0.7 ml/min g kidney wt in controls, experimental values given are those determined 10 minutes after termination of 100 micrograms/ml RVV admixture), glomerular filtration rate (GFR 141 +/- 23 vs. 626 +/- 72 microliters/min g kidney wt) and absolute reabsorption of sodium (TNa 8 +/- 1.7 vs. 79 +/- 9 mumol/min g kidney wt), and an increased fractional excretion of sodium (FENa 60 +/- 7 vs. 8 +/- 0.8%) and water (FEH2O 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 micrograms/ml. In epithelial LLC-PK1 and MDCK cell cultures only extremely high doses of RVV (> 600 and 800 micrograms/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.

Animal toxins and the kidney

“…44 In an experimental study, Russell's viper venom caused lysis of vascular smooth muscle cells, mesangiolysis and tubular degeneration with cellular detachment from the basement membrane. 45 In isolated renal perfusion studies, Russell's viper venom reduced the potential difference across the cell membrane of proximal tubule cells and decreased the tubular reabsorption of sodium in a dose-dependent fashion. 46,47 Peptides present in the venom of the Eastern green mamba snake (Dendroaspis angusticeps), 48 the South American coral snake (Micrurus corallinus) 49 and the jararaca pit viper 50 can cause natriuresis by decreasing sodium reabsorption in the distal nephron, through activation of cyclic GMP.…”

Bothrops moojeni snake venom-induced renal glomeruli changes in rat.

“…26 This ionic barrier of glomerular filtration was shown to be destroyed by Vipera russelli venom in isolated rat kidneys. 27 Several proteins, including type IV collagen, laminin, entactin, and heparin sulfate proteoglycan are common components of basement membranes, although there are important tissue-to-tissue differences in the relative proportion. 28,29 The strong attachment of podocytes to the GBM is based on ␣ 3 -␤ 1 integrin-fibronectin-laminin interactions.…”

Enzymatic and toxinological activities of Hypnale hypnale (hump-nosed pit viper) venom and its fractionation by ion exchange high performance liquid chromatography

“…Hematoxic and myotoxic venoms from viperids or crotalids are a rich source of enzymes that include phospholipases, endopeptidases, L-amino acid oxidases and metalloproteases which can directly cause cellular damage and kidney injury (60,61). In the present study, D. russellii venom from Myanmar was administered to the positive control group (DV group) to produce acute kidney injury as the venom was known to be highly nephrotoxic (62)(63)(64)(65).…”