Evaluation of organic nephrotoxins in rabbit renal cortical slices

An in vitro cortical-slice system was used to assess the toxicity of several organic nephrotoxins that require transport and/or bioactivation in order to induce toxicity. The toxins cephaloridine, hexachlorobutadiene, S-(1,2-dichlorovinyl)-l-cysteine and gentamicin all produce site-specific proximal tubular injury when administered in vivo. Damage was assessed in vitro by observing alterations in intracellular potassium, intracellular lactate dehydrogenase, and organic anion and cation accumulation. Histopathology was studied to assess the localization of injury. All four compounds produced dose- and time-dependent decreases in the biochemical parameters as well as site-specific lesions in the S₃ region. The results illustrate the usefulness of renal cortical slices in acute studies of organic nephrotoxins.