© 1988 Oxford University Press
research-article |
The Use of Reneal Cortical Slices from the Fischer 344 Rat as an in vitro Model to Evaluate Nephrotoxicity1
Laboratory of Experimental Therapeutics and Metabolism, Developmental Therapeutics Program Division of Cancer Treatement, National Cancer Institute, National Institutes of Health Bethesda, Maryland 20205
Received August 17, 1987; accepted February 11, 1988
The Use of Renal Cortical Slices from the Fischer 344 Rat as an in Vitro Model to Evaluate Nephrotoxicity. Smith, J. H. (1988). Fundam Appl. Pharmacol 11, 132–142. The toxicity of several classical acute nephrotoxicants was evaluated in an in vitro system using renal cortical slices prepared from adult male Fischer 344 rats. Gentamicin, cephaloridine, 4-ipomeanol, potassium dichromate (K2Cr2(>7), mercuric chloride (HgCl2), carbon tetrachloride (CCU), and hex-achlorobutadiene (HCBD) were preincubated with slices for 2 hr at 37°C at concentrations ranging from 1 × 10-6 to 1 × 10-1 m. Following preincubation, slices were removed, rinsed in medium lacking the nephrotoxicant, and subsequently incubated for 90 min at 25°C for physiological assessment of proximal tubular functions. Using a single preparation, slices were monitored for organic ion accumulation, gluconeogenesis, lipid peroxidation, and total glutathi-one (reduced and oxidized) concentrations. In addition, preincubation and incubation media were assessed for the presence of renal enzymes originating from brush border, cytosol, and lysosomes. The relative degree of toxicity in this model was consistent with nephrotoxic potency in vivo where HgCl2, K2Cr2C>7 > HCBD > CCl4, cephaloridine > gentamicin > 4-ipomeanol. Effects on organic ion accumulation, gluconeogenesis, and glutathione concentrations occurred simultaneously for each toxicant. Toxicants produced different effects on enzyme release and malondialdehyde formation. These results suggest that toxicity produced in vitro is representative of in vivo nephrotoxicity and support the further use of this model to evaluate mechanisms Of nephrotoxicity.