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五氯苯酚会导致氧化还原失衡,抑制刷状缘膜和代谢酶,造成大鼠肾脏 DNA 损伤和组织学改变。

Pentachlorophenol causes redox imbalance, inhibition of brush border membrane and metabolic enzymes, DNA damage and histological alterations in rat kidney.

机构信息

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

Department of Anatomy, J. N. Medical College, Aligarh Muslim University, Aligarh 202002, U.P., India.

出版信息

Pestic Biochem Physiol. 2023 Feb;190:105318. doi: 10.1016/j.pestbp.2022.105318. Epub 2022 Dec 16.

Abstract

Pentachlorophenol (PCP) is a synthetic organochlorine compound that is widely used in biocide and pesticide industries, and in preservation of wood, fence posts, cross arms and power line poles. Humans are usually exposed to PCP through air, contaminated water and food. PCP enters the body and adversely affects liver, gastrointestinal tract, kidney and lungs. PCP is a highly toxic class 2B or probable human carcinogen that produces large amount of reactive oxygen species (ROS) within cells. This work aimed to determine PCP-induced oxidative damage in rat kidney. Adult rats were given PCP (25, 50, 100, 150 mg/kg body weight), in corn oil, once a day for 5 days while control rats were given similar amount of corn oil by oral gavage. PCP increased hydrogen peroxide level and oxidation of thiols, proteins and lipids. The antioxidant status of kidney cells was compromised in PCP treated rats while enzymes of brush border membrane (BBM) and carbohydrate metabolism were inhibited. Plasma level of creatinine and urea was also increased. Administration of PCP increased DNA fragmentation, cross-linking of DNA to proteins and DNA strand scission in kidney. Histological studies supported biochemical findings and showed significant damage in the kidneys of PCP-treated rats. These changes could be due to redox imbalance or direct chemical modification by PCP or its metabolites. These results signify that PCP-induced oxidative stress causes nephrotoxicity, dysfunction of BBM enzymes and DNA damage.

摘要

五氯苯酚(PCP)是一种合成有机氯化合物,广泛用于生物杀灭剂和农药行业,以及木材、围栏柱、横臂和输电线杆的防腐。人类通常通过空气、受污染的水和食物接触到 PCP。PCP 进入人体后会对肝脏、胃肠道、肾脏和肺部造成不良影响。PCP 是一种剧毒的 2B 类物质或可能的人类致癌物,它会在细胞内产生大量的活性氧(ROS)。本研究旨在确定 PCP 对大鼠肾脏的氧化损伤作用。成年大鼠每天以玉米油为载体灌胃给予 PCP(25、50、100、150mg/kg 体重),连续 5 天,而对照组大鼠给予相同体积的玉米油。PCP 增加了过氧化氢水平和巯基、蛋白质和脂质的氧化。PCP 处理大鼠的肾脏细胞抗氧化状态受损,而刷状缘膜(BBM)和糖代谢的酶被抑制。PCP 还增加了血浆肌酐和尿素的水平。PCP 给药增加了肾脏中的 DNA 片段化、DNA 与蛋白质的交联和 DNA 链断裂。组织学研究支持了生化发现,并显示 PCP 处理大鼠的肾脏有明显损伤。这些变化可能是由于氧化还原失衡或 PCP 或其代谢物的直接化学修饰所致。这些结果表明,PCP 诱导的氧化应激导致了肾毒性、BBM 酶功能障碍和 DNA 损伤。

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