Suzuki T, Sasaki H, Komatsu M, Miyazawa T, Isono H
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Biol Pharm Bull. 1994 Oct;17(10):1351-4. doi: 10.1248/bpb.17.1351.
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.
在分离的大鼠肝细胞中检测了1,3 - 二氯丙烯诱导的时间和剂量依赖性毒性及脂质过氧化作用。采用化学发光检测的高效液相色谱法（CL - HPLC）测定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。作为毒理学参数的乳酸脱氢酶（LDH）释放量，在1 mM 1,3 - 二氯丙烯孵育90分钟后以及5 mM孵育60分钟后分别显著增加。细胞内PCOOH和PEOOH含量，在1 mM 1,3 - 二氯丙烯孵育90分钟后增加，在5 mM时，PCOOH孵育15分钟后增加，PEOOH孵育30分钟后增加。细胞磷脂氢过氧化物的增加先于细胞毒性。预先用d,1 - α - 生育酚（α - toc.）孵育可有效预防肝毒性，并同时预防膜磷脂过氧化。总之，磷脂过氧化先于细胞毒性，且α - toc.可有效预防细胞毒性。这些结果表明，膜磷脂的过氧化降解是1,3 - 二氯丙烯导致细胞毒性的主要原因之一。
