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口服五氯苯酚会损害抗氧化系统,抑制刷状缘膜酶,导致大鼠肠道DNA损伤和组织学变化。

Oral administration of pentachlorophenol impairs antioxidant system, inhibits enzymes of brush border membrane, causes DNA damage and histological changes in rat intestine.

作者信息

Maheshwari Nikhil, Khan Aijaz Ahmed, Ali Asif, Mahmood Riaz

机构信息

Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, U.P., India.

Departments of Anatomy, J. N. Medical College and Hospital, Aligarh Muslim University, Aligarh 202002, U.P., India.

出版信息

Toxicol Res (Camb). 2022 Jun 28;11(4):616-627. doi: 10.1093/toxres/tfac035. eCollection 2022 Aug.

Abstract

Pentachlorophenol (PCP) is a broad spectrum biocide that has many domestic and industrial applications. PCP enters the environment due to its wide use, especially as a wood preservative. Human exposure to PCP is through contaminated water and adulterated food products. PCP is highly toxic and is classified as class 2B or probable human carcinogen. In this study, we explored the effect of PCP on rat intestine. Adult rats were orally given different doses of PCP (25-150-mg/kg body weight/day) in corn oil for 5 days, whereas controls were given similar amount of corn oil. The rats were sacrificed 24 h after the last treatment. A marked increase in lipid peroxidation, carbonyl content, and hydrogen peroxide level was seen. The glutathione and sulfhydryl group content was decreased in all PCP treated groups. This strongly suggests the generation of reactive oxygen species (ROS) in the intestine. PCP administration suppressed carbohydrate metabolism, inhibited enzymes of brush border membrane (BBM), and antioxidant defense system. It also led to increase in DNA damage, which was evident from comet assay, DNA-protein cross-linking, and DNA fragmentation. Histological studies supported the biochemical results showing marked dose-dependent tissue damage in intestines from PCP treated animals. This study reports for the first time that oral administration of PCP induces ROS, impairs the antioxidant system, damages DNA, and alters the enzyme activities of BBM and metabolic pathways in rat intestine.

摘要

五氯苯酚(PCP)是一种具有广泛家用和工业用途的广谱杀菌剂。由于其广泛使用,尤其是作为木材防腐剂,PCP进入了环境。人类通过受污染的水和掺假食品接触PCP。PCP具有高毒性,被归类为2B类或可能的人类致癌物。在本研究中,我们探讨了PCP对大鼠肠道的影响。成年大鼠经口给予不同剂量的PCP(25 - 150毫克/千克体重/天),溶于玉米油中,持续5天,而对照组给予等量的玉米油。在最后一次处理后24小时处死大鼠。结果发现脂质过氧化、羰基含量和过氧化氢水平显著增加。所有PCP处理组的谷胱甘肽和巯基含量均降低。这强烈表明肠道中产生了活性氧(ROS)。给予PCP抑制了碳水化合物代谢,抑制了刷状缘膜(BBM)的酶以及抗氧化防御系统。它还导致DNA损伤增加,这从彗星试验、DNA - 蛋白质交联和DNA片段化中可以明显看出。组织学研究支持了生化结果,显示PCP处理动物的肠道存在明显的剂量依赖性组织损伤。本研究首次报道口服PCP会诱导ROS产生,损害抗氧化系统,损伤DNA,并改变大鼠肠道中BBM的酶活性和代谢途径。

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