五氯苯酚及其代谢物四氯-1,2-对苯二酚和四氯-1,4-苯醌对HepG2细胞的毒性比较

Ilka Elizma Schroeder, J. J. V. Tonder, V. Steenkamp
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引用次数: 5

摘要

有机氯化合物五氯酚(PCP)被列为有害物质。其代谢物四氯-1,2-对苯二酚(TCHQ)已在职业暴露的受试者中检测到,在生理条件下很容易转化为四氯-1,4-苯醌(TCBQ)。先前的危害特征已经确定肝脏是大鼠和狗的PCP毒性的靶器官,并且肝脏是母体化合物代谢的主要部位,这引起了人们对PCP代谢物可能对肝脏产生影响的关注。虽然PCP的肝毒性作用已被描述,但其代谢物对肝细胞功能的影响尚不清楚。研究这些代谢物对肝细胞的影响可以提供有关这些化合物对肝脏本身的影响的有价值的信息,并暗示可以预期的毒性的临床表现。因此,本研究的目的是评估PCP、TCHQ和TCBQ对以下细胞参数的影响:细胞活力、线粒体膜电位和细胞内ROS形成,作为肝细胞稳态的指标。PCP及其代谢物、TCHQ和TCBQ均可降低细胞活力,ic50分别为68.05、129.40和144.00∝M。这三种化合物都引起线粒体去极化,暴露于TCHQ和TCBQ后影响更深远。PCP不诱导ROS生成,而TCHQ和TCBQ则产生大量ROS。本研究结果提示PCP在肝细胞中的毒性机制与其代谢物TCHQ和TCBQ不同。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparative toxicity of pentachlorophenol with its metabolites tetrachloro-1,2-hydroquinone and tetrachloro-1,4-benzoquinone in HepG2 cells
The organochlorine compound, pentachlorophenol (PCP), is classified as a hazardous substance. Its metabolite, tetrachloro-1,2-hydroquinone (TCHQ), has been detected in occupationally-exposed subjects and can readily be converted to tetrachloro-1,4-benzoquinone (TCBQ) under physiological conditions. Hazard characterization has previously identified the liver as the target organ of PCP toxicity in rats and dogs and as the liver is the major site of metabolism of the parent compound, this raises concern for the effects that the metabolites of PCP may have on the liver. Although the hepatotoxic effects of PCP have been described, less is known about the effects of its metabolites on hepatocyte function. Studying the effects of these metabolites on hepatocytes may provide valuable information regarding the effects that these compounds could exert on the liver itself and allude to the clinical manifestations of toxicity that can be expected. The aim of this study was therefore to assess the effect of PCP, TCHQ and TCBQ on the following cellular parameters: cell viability, mitochondrial membrane potential and intracellular ROS formation, as indicators of hepatocyte homeostasis. Both PCP and its metabolites, TCHQ and TCBQ decreased cell viability with IC 50 of 68.05, 129.40 and 144.00 ∝M, respectively. All three compounds caused mitochondrial depolarization, with the effect being more profound following exposure to TCHQ and TCBQ. PCP did not induce any ROS generation, whereas TCHQ and TCBQ produced extensive ROS. Findings from this study suggest that in hepatocytes the mechanism of toxicity of PCP differs from that of its metabolites, TCHQ and TCBQ.
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