Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Clifton Boulevard, Nottingham NG7 2UH, UK.
Environ Toxicol Pharmacol. 1996 Feb 15;1(1):39-43. doi: 10.1016/1382-6689(95)00007-0.
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.
人类接触二氯丙醇会导致暴发性肝坏死。这些化合物在大鼠中也显示出肝毒性。在这项研究中，1,3-二氯丙醇而不是 2,3-二氯丙醇被证明对大鼠肝细胞 24 小时培养物有毒。该毒性可通过用细胞色素 P450 抑制剂预处理培养物来抑制，并且通过先前耗尽细胞内谷胱甘肽来增强。此外，在等摩尔浓度下，两种异构体均显示出谷胱甘肽耗竭，尽管 1,3-异构体的耗竭程度更大。1,3-二氯丙醇还耗尽了 ATP 并降低了线粒体膜电位。细胞色素 P450 抑制剂可抑制对 ATP、谷胱甘肽和膜电位的影响。结论是，1,3-二氯丙醇的毒性是由细胞色素 P450 介导的，涉及谷胱甘肽耗竭和线粒体功能丧失。
