Cytotoxicity of 1,3-dichloropropene and cellular phospholipid peroxidation in isolated rat hepatocytes, and its prevention by alpha-tocopherol.
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,1-alpha-tocopherol (alpha-toc.) accompanied by prevention of the membrane phospholipid peroxidation. In conclusion, the peroxidation of phospholipid preceded cytotoxicity, and cytotoxicity was effectively prevented by alpha-toc. These results indicated that the peroxidative degradation of membrane phospholipid is one of the main causes of cytotoxicity by 1,3-dichloropropene.
Suzuki
T
T
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Sasaki
H
H
Komatsu
M
M
Miyazawa
T
T
Isono
H
H
D000498:Allyl Compounds / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D014810:Vitamin E / Q000494:pharmacology*
D000498:Allyl Compounds; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C057590:phosphatidylcholine hydroperoxide; C027850:phosphatidylethanolamine hydroperoxide; D014810:Vitamin E; C023891:1,3-dichloro-1-propene; D007770:L-Lactate Dehydrogenase