The nephrotoxicity of hexachloro-1:3-butadiene in the rat: Studies of organic anion and cation transport in renal slices and the effect of monooxygenase inducers

Abstract

Administration of a single dose of hexachloro-1:3-butadiene (HCBD) to adult rats produced renal tubular necrosis which was reversed after about 14 days. Slices of renal cortex from HCBD-treated rats were less able to accumulate the organic anion, p-aminohippurate (PAH), whereas accumulation of the organic cation, tetraethylammonium (TEA), was unaffected. The rate of efflux of both of these ions from slices of renal cortex from HCBD-treated rats was unaltered. From these data it is concluded that the renal organic anion uptake system was selectively damaged by HCBD treatment, while the organic cation uptake system was unaffected. Treatment of animals with probenecid, an inhibitor of renal organic anion transport, did not alter the nephrotoxicity. Prior administration of a number of inducers or an inhibitor (piperonyl butoxide) of hepatic and/or renal microsomal monooxygenases did not alter the susceptibility of the kidney to HCBD-induced injury. Treatment of animals with diethylmaleate, a compound which decreases tissue nonprotein sulfhydryl content, markedly potentiated the nephrotoxicity of HCBD and led to crystalline deposits in the tubular lumen, suggesting tubular occlusion. These results indicate that cytochrome P-450-mediated reactions do not appear to play a major role in this type of renal toxicity, whereas the role of nonprotein sulfhydryl depletion in the nephrotoxicity needs further investigation.