Cytotoxicity of organochlorine pesticides and lipid peroxidation in isolated rat hepatocytes.
The cytotoxicity and lipid peroxidation of pesticides containing a halogen group were examined in isolated rat hepatocytes. We examined 9 pesticides of 3 different representative chemical families, chlorinated aromatic fungicides (pentachlorophenol (PCP), pentachloronitrobenzene (PCNB), chlorothalonil, fthalide), polyhaloalkylated thio fungicides (dichlofluanid, captan) and diphenyl ether herbicide (2,4-dichlorophenyl 4-nitrophenyl ether (NIP), 4-nitrophenyl2,4,6-trichlorophenyl ether (CNP), chlomethoxynil). The contents of the hydroperoxides in phospholipid, phosphatidylcholine hydroperoxide (PCOOH) and phosphatidylethanolamine hydroperoxide (PEOOH) were determined by the HPLC-chemiluminescence (CL-HPLC) method, which is sensitive and specific for lipid hydroperoxide. Chlorothalonil, dichlofluanid and captan were the most potent cytotoxicants evaluated by lactate dehydrogenase (LDH) leakage. PCP, NIP and CNP exhibited intermediate cytotoxicity. PCNB, fthalide and chlomethoxynil showed low cytotoxicity. The cellular phospholipid hydroperoxide (PCOOH and PEOOH) levels were remarkably increased by chlorothalonil (PCOOH, 23 times and PEOOH, 7 times), dichlofluanid (PCOOH, 523 times and PEOOH, 22 times) and captan (PCOOH, 518 times and PEOOH, 16 times) as compared with the control group. The PCOOH content was slightly increased by PCP (4.8 times) and NIP (6.3 times), whereas the other 4 pesticides did not change the phospholipid hydroperoxide level. Severe cytotoxicity was observed with a remarkable increase of phospholipid hydroperoxide by chlorothalonil, dichlofluanid and captan.
Suzuki
T
T
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Komatsu
M
M
Isono
H
H
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; 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; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D007306:Insecticides; D017392:Thiobarbituric Acid Reactive Substances; D007770:L-Lactate Dehydrogenase; D005978:Glutathione