Katoh T, Haratake J, Nakano S, Kikuchi M, Yoshikawa M, Arashidani K
School of Health Sciences, University of Occupational & Environmental Health, Kitakyushu, Japan.
Ind Health. 1998 Oct;36(4):318-23. doi: 10.2486/indhealth.36.318.
A rare outbreak of acute hepatic damage in workers exposed to dichloropropanols (DCPs) was reported recently. The purpose of the present study is to examine the effects of DCPs on various organs, the dose dependency and the pathogenetic potential of DCP hepatotoxicity. A single intraperitoneal injection was given to six groups of rats with 0.2 ml of 20% ethanol (control), or 1/8 x, 1/4 x, 1/2 x, 1 x, and 2 x LD50 (0.11 ml/kg) of 1,3-dichloro, 2-propanol (DC2P) diluted in 20% ethanol. After blood samplings, all organs were subjected to histologic examinations with light and electron microscopes. Fresh liver tissues from further 4 control and 4 experimental rats sacrificed 6 hours after the injection of 20% ethanol and 1 x LD50 of DC2P were homogenized and subjected to evaluate lipid peroxidation, glutathione S-transferase activity and reduced glutathione contents in the liver. The rats administered with only ethanol or 1/8 and 1/4 LD50 of DC2P showed no serological or histopathological abnormalities. Marked elevation of serum glutamate pyruvate transaminase (SGPT) with a diffuse massive necrosis of the liver cells were noted in all rats of both the 1 x and 2 x LD50 groups, and irregular zonal necroses were found in 3 of 4 rats injected with 1/2 LD50. There were no serious toxic changes in other organs. Hepatic malondialdehyde level was significantly increased, associated with decreases of liver glutathione S-transferase activity and reduced glutathione content. It was concluded that the serious DC2P-toxicity was mainly found in the livers, dose dependently, and one of the causative mechanisms of this hepatotoxicity might be the lipid peroxidation.
最近报道了一起接触二氯丙醇（DCPs）的工人中罕见的急性肝损伤暴发事件。本研究的目的是研究DCPs对各器官的影响、剂量依赖性以及DCP肝毒性的致病潜力。给六组大鼠进行单次腹腔注射，分别注射0.2 ml 20%乙醇（对照组），或用20%乙醇稀释的1,3 - 二氯 - 2 - 丙醇（DC2P）的1/8 x、1/4 x、1/2 x、1 x和2 x LD50（0.11 ml/kg）。采血后，所有器官均用光学显微镜和电子显微镜进行组织学检查。另外取4只注射20%乙醇的对照大鼠和4只注射1 x LD50 DC2P的实验大鼠，在注射后6小时处死，取新鲜肝脏组织匀浆，评估肝脏中的脂质过氧化、谷胱甘肽S - 转移酶活性和还原型谷胱甘肽含量。仅给予乙醇或1/8和1/4 LD50 DC2P的大鼠未出现血清学或组织病理学异常。1 x和2 x LD50组的所有大鼠均出现血清谷丙转氨酶（SGPT）显著升高，伴有肝细胞弥漫性大片坏死，注射1/2 LD50的4只大鼠中有3只出现不规则带状坏死。其他器官未出现严重毒性变化。肝脏丙二醛水平显著升高，同时肝脏谷胱甘肽S - 转移酶活性和还原型谷胱甘肽含量降低。结论是严重的DC2P毒性主要发生在肝脏，具有剂量依赖性，这种肝毒性的致病机制之一可能是脂质过氧化。
