Cytotoxicity of chlorinated hydrocarbons and lipid peroxidation in isolated rat hepatocytes.
The effects of 11 chlorinated hydrocarbons on toxicological parameters and lipid peroxidation were examined in cultured rat hepatocytes. The cytotoxicity was evaluated by measuring the lactate dehydrogenase (LDH) released and the protein amount in cells attached to culture dishes. Phosphatidylcholine hydroperoxide (PCOOH) and phosphatidylethanolamine hydroperoxide (PEOOH) levels were determined by HPLC with chemiluminescence detection (CL-HPLC). Severe cytotoxicity was observed under the presence of the carbon tetrachloride, 1,1,1-trichloroethane, tetrachloroethylene and 1,3-dichloropropene in a concentration of 10 mM. The cellular PCOOH and PEOOH levels were remarkably increased (more than 4 times) by adding these 4 chlorinated hydrocarbons. The other 7 chlorinated hydrocarbons examined did not cause any change on the cellular phospholipid hydroperoxide levels, and showed lower or no cytotoxicity at a concentration of 10 mM. The peroxidative degradation of membrane phospholipids may play an important role in causing the cytotoxicity of some chlorinated hydrocarbons.
Suzuki
T
T
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Nezu
K
K
Sasaki
H
H
Miyazawa
T
T
Isono
H
H
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008163:Luminescent Measurements; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005227:Fatty Acids; D006843:Hydrocarbons, Chlorinated; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C057590:phosphatidylcholine hydroperoxide; C027850:phosphatidylethanolamine hydroperoxide; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase