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硒对邻甲酚诱导大鼠癌相关凋亡基因过表达的保护作用。

Protective role of selenium against over-expression of cancer-related apoptotic genes induced by o-cresol in rats.

机构信息

Cell Biology Department, National Research Centre, Dokki, Giza, Egypt.

出版信息

Arh Hig Rada Toksikol. 2011 Jun;62(2):121-9. doi: 10.2478/10004-1254-62-2011-2074.

DOI:10.2478/10004-1254-62-2011-2074
PMID:21705299
Abstract

Cresols are monomethyl derivatives of phenol frequently used as solvents and intermediates in the production of disinfectants, fragrances, pesticides, dyes, and explosives, which is probably why they are widely distributed in the environment. General population may be exposed to cresols mainly through inhalation of contaminated air. In this study we evaluated the toxicological effects of o-cresol on differential gene expression profile of rat liver and prostate. Experiments were conducted on 80 male rats, 60 of which were exposed to o-cresol (1.5 g kg-1, 5 g kg-1, or 15 g kg-1) through feed for 8 weeks. Three groups of rats were supplemented with 0.1 mg kg-1 selenium (Se, in the form of, sodium selenite) in addition to o-cresol to evaluate its effectiveness against o-cresol toxicity. Control group received neither o-cresol nor Se, while one group received Se alone. Survival was similar between the exposed and control animals. Rats exposed to 15 g kg-1 of o-cresol showed a 16 % loss in body weight by the end of the study, which may have been related to o-cresol making feed unpalatable at this concentration. Liver and prostate tissue samples were collected at the end of the treatment. mRNA analysis revealed that apoptotic genes (CYP3A, COX-2, PPARγ, BAX, BCL2, AKT-1, and PKCα) related to cancer were up-regulated in liver and prostate tissues isolated from groups exposed to 5 g kg-1 and 15 g kg-1o-cresol in comparison to control. Changes in gene expression profile were prevented when rats were supplemented with Se. The exact mechanisms underlying its protective effect remain to be clarified by future studies.

摘要

甲酚是苯酚的单甲基衍生物,常被用作消毒剂、香料、农药、染料和炸药的溶剂和中间体,这可能就是它们在环境中广泛分布的原因。一般人群主要通过吸入污染的空气接触到甲酚。在这项研究中,我们评估了邻甲酚对大鼠肝脏和前列腺差异基因表达谱的毒理学影响。实验在 80 只雄性大鼠中进行,其中 60 只通过饲料暴露于邻甲酚(1.5 g/kg、5 g/kg 或 15 g/kg)8 周。三组大鼠除了邻甲酚外,还补充了 0.1 mg/kg 的硒(以亚硒酸钠的形式),以评估其对邻甲酚毒性的有效性。对照组既不接受邻甲酚也不接受硒,而一组仅接受硒。暴露组和对照组动物的存活率相似。在研究结束时,暴露于 15 g/kg 邻甲酚的大鼠体重下降了 16%,这可能与邻甲酚在该浓度下使饲料变得不可口有关。在治疗结束时收集了肝脏和前列腺组织样本。mRNA 分析显示,与对照组相比,暴露于 5 g/kg 和 15 g/kg 邻甲酚的大鼠肝脏和前列腺组织中与癌症相关的凋亡基因(CYP3A、COX-2、PPARγ、BAX、BCL2、AKT-1 和 PKCα)上调。当大鼠补充硒时,基因表达谱的变化得到了预防。其保护作用的确切机制仍有待未来的研究来阐明。

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