The Hepatotoxicity and Nephrotoxicity of Hexachlorobutadiene

Abstract

Hexachloro 1:3 butadiene (HCBD) is formed as a by-product during the chlorination of hydrocarbons for the manufacture of chlorinated ethylenes and carbon tetrachloride. Administration of HCBD (300 mg/kg, ip) to rats produces a mild reversible hydropic swelling of the liver. This change is associated with a swelling of mitochondria in hepatocytes located in the periportal region of the liver. However, the major target organ for toxicity is the kidney where HCBD produces necrosis of the pars recta of the proximal tubule. Treatment of rats with inducers or inhibitors of hepatic and/or renal drug metabolising enzymes followed by HCBD administration does not markedly alter HCBD-induced liver or kidney injury. In male rats, HCBD causes a depletion of hepatic but not renal non-protein sulphydryl content (NP-SH) and pretreatment of animals with diethylmaleate, which reduces tissue glutathione content, markedly enhances the nephrotoxicity of HCBD. Our findings to date indicate that glutathione plays a protective role against HCBD-induced renal tubular necrosis which suggests a metabolic activation reaction may be involved in the nephrotoxicity.