Suzuki T, Komatsu M, Isono H
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Biol Pharm Bull. 1997 Mar;20(3):271-4. doi: 10.1248/bpb.20.271.
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.
在分离的大鼠肝细胞中检测了含卤素基团农药的细胞毒性和脂质过氧化作用。我们检测了3个不同代表性化学家族的9种农药，包括氯代芳香族杀菌剂（五氯苯酚（PCP）、五氯硝基苯（PCNB）、百菌清、酞菌酯）、多卤代烷基硫代杀菌剂（二氯氟苯胺、克菌丹）和二苯醚除草剂（2,4 - 二氯苯基4 - 硝基苯基醚（NIP）、4 - 硝基苯基2,4,6 - 三氯苯基醚（CNP）、氯甲氧基腈）。采用对脂质氢过氧化物敏感且特异的高效液相色谱 - 化学发光（CL - HPLC）法测定磷脂中氢过氧化物、磷脂酰胆碱氢过氧化物（PCOOH）和磷脂酰乙醇胺氢过氧化物（PEOOH）的含量。通过乳酸脱氢酶（LDH）泄漏评估，百菌清、二氯氟苯胺和克菌丹是最有效的细胞毒性剂。PCP、NIP和CNP表现出中等细胞毒性。PCNB、酞菌酯和氯甲氧基腈显示出低细胞毒性。与对照组相比，百菌清（PCOOH增加23倍，PEOOH增加7倍）、二氯氟苯胺（PCOOH增加523倍，PEOOH增加22倍）和克菌丹（PCOOH增加518倍，PEOOH增加16倍）使细胞磷脂氢过氧化物（PCOOH和PEOOH）水平显著升高。PCP（4.8倍）和NIP（6.3倍）使PCOOH含量略有增加，而其他4种农药未改变磷脂氢过氧化物水平。观察到百菌清、二氯氟苯胺和克菌丹具有严重的细胞毒性，同时磷脂氢过氧化物显著增加。
