Toxicity of dichloropropanols in rat hepatocyte cultues

Exposure of humans to dichloropropanols has been shown to result in fulminant hepatic necrosis. These compounds have also been shown to be hepatotoxic in rats. In this study, 1,3-dichloropropanol, but not 2,3-dichloropropanol, was shown to be toxic to 24 h cultures of rat hepatocytes. The toxicity was inhibited by pre-treatment of cultures with a cytochrome P450 inhibitor and enhanced by prior depletion of cellular glutathione. In addition, at equimolar concentrations both isomers were shown to deplete glutathione, although the extent of depletion was greater with the 1,3-isomer. 1,3-Dichloropropanol also depleted ATP and reduced the mitochondrial membrane potential. The effects on ATP, glutathione and membrane potential could be inhibited by the cytochrome P450 inhibitor. It is concluded that the toxicity of 1,3-dichloropropanol is mediated by cytochrome P450 and involves depletion of glutathione and loss of mitochondrial function.