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六氯苯(HCB)在离体灌注大鼠肝脏中的代谢

Metabolism of hexachlorobenzene (HCB) in the isolated perfused rat liver.

作者信息

Ingebrigtsen K, Skaare J U, Nafstad I, Grave K, Førde M

出版信息

Gen Pharmacol. 1986;17(1):19-24. doi: 10.1016/0306-3623(86)90005-4.

Abstract

The metabolism of HCB in the isolated perfused rat liver was studied by administration of [14C]HCB diluted with unlabelled HCB at a total dose of 0.1 mg HCB/ml perfusate. Metabolites in bile, perfusate and liver were studied by GLC-mass spectrometry. Histological examination of the livers showed that no hepatic necrosis had developed, although there was a slight increase in ASAT and ALAT in the perfusate and about 50% decrease in hepatic glutathione. About 0.15% of administered radioactivity was recovered in the bile within 2 hr. In the bile, HCB together with the metabolites pentachlorothiophenol and pentachlorophenol, were identified and accounted for about 20% of the radioactivity excreted. In addition, eleven metabolites with 4 or 5 chlorines were isolated. In the perfusate and in the liver, unchanged HCB was responsible for most of the radioactivity. Traces of pentachlorothiophenol and pentachlorophenol were identified in the perfusate and the liver, respectively.

摘要

通过向灌注液中加入总剂量为0.1毫克六氯苯/毫升灌注液(其中[14C]六氯苯用未标记的六氯苯稀释),研究了六氯苯在离体灌注大鼠肝脏中的代谢情况。采用气相色谱-质谱联用技术研究胆汁、灌注液和肝脏中的代谢产物。肝脏组织学检查表明,尽管灌注液中谷草转氨酶(ASAT)和谷丙转氨酶(ALAT)略有升高,肝脏谷胱甘肽含量下降约50%,但未出现肝坏死。给药后2小时内,约0.15%的放射性物质在胆汁中回收。在胆汁中,已鉴定出六氯苯及其代谢产物五氯硫酚和五氯酚,它们约占排泄放射性物质的20%。此外,还分离出了11种含4个或5个氯原子的代谢产物。在灌注液和肝脏中,大部分放射性物质来自未变化的六氯苯。在灌注液和肝脏中分别鉴定出了痕量的五氯硫酚和五氯酚。

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