Cytotoxicity of 1,3-Dichloropropene and Cellular Phospholipid Peroxidation in Isolated Rat Hepatocytes, and Its Prevention by α-Tocopherol

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1,3-Dichloropropene induced time- and dose-dependent toxicity and lipid peroxidation were examined in isolated rat hepatocytes. HPLC method with chemiluminescence detection (CL-HPLC) was employed to determine phosphatidylcholine hydroperoxide (PCOOH) and phosphatidylethanolamine hydroperoxide (PEOOH) contents. The release of lactate dehydrogenase (LDH) as a toxicological parameter was significantly increased after 90 min incubation at 1 mM of 1,3-dichloropropene and after 60 min incubation at 5 mM, respectively. The cellular PCOOH and PEOOH contents were increased after 90 min incubation at 1 mM of 1,3-dichloropropene, and after 15 min for PCOOH and 30 min for PEOOH at 5 mM, respectively. The increase of cellular phospholipid hydroperoxide preceded the cytotoxicity. Hepatotoxicity was effectively prevented by preincubation with d, l-α-tocopherol (α-toc.) accompanied by prevention of the membrane phospholipid peroxidation. In conclusion, the peroxidation of phospholipid preceded cytotoxicity, and cytotoxicity was effectively prevented by α-toc. These results indicated that the peroxidative degradation of membrane phospholipid is one of the main causes of cytotoxicity by 1,3-dichloropropene.
社団法人日本薬学会の論文
1994-10-15