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六氯萘(HxCN)的毒性及其对大鼠 CYP1A 的诱导作用。

Toxicity of hexachloronaphthalene (HxCN) and induction of CYP 1A in rats.

机构信息

Department of Toxicology, Faculty of Pharmacy, Medical University, Muszynskiego 1, 90-151 Lodz, Poland.

出版信息

Ecotoxicol Environ Saf. 2010 Feb;73(2):196-205. doi: 10.1016/j.ecoenv.2009.08.018. Epub 2009 Sep 26.

Abstract

The aim of the study was to investigate the toxicity of hexachloronaphthalene (HxCN) and its effect on cytochrome P-450 in rats and to make a comparison between HxCN and tetrachloronaphthalene (TeCN), an inactive congener. Our study provided evidence that the anorectic effect, with concurrent significant increase in relative liver mass was the most spectacular symptom of the toxic effect of hexachloronaphthalene in the rats after its single (250mg/kg) and repeated (1 and 10mg/kg) administration. Regardless of the kind of the experiment (acute or subacute toxicity), dose-dependent increase in lipid peroxidation in the liver was also observed, which may indicate that HxCN most probably generates oxidative stress in this organ. It was also observed that HxCN is a very strong inducer of cytochrome P-450, especially of CYP 1A, which is the most sensitive biomarker of exposure to this congener. In this study, LOAEL is 1mg HxCN/kgb.w.

摘要

本研究旨在探究六氯萘(HxCN)的毒性及其对大鼠细胞色素 P-450 的影响,并将其与四氯萘(TeCN)这一惰性同系物进行比较。我们的研究结果表明,在大鼠单次(250mg/kg)和重复(1 和 10mg/kg)给予 HxCN 后,其最显著的毒性作用是引起厌食症,同时相对肝脏质量显著增加。无论实验类型(急性或亚急性毒性)如何,肝脂质过氧化均呈剂量依赖性增加,这可能表明 HxCN 很可能在该器官中产生氧化应激。此外,还观察到 HxCN 是细胞色素 P-450 的强诱导剂,尤其是 CYP 1A,它是暴露于该同系物的最敏感生物标志物。在本研究中,HxCN 的 LOAEL 为 1mg/kgbw。

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