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铜中毒时器官损伤的时间动力学:大鼠模型中的组织病理学相关性

Temporal kinetics of organ damage in copper toxicity: A histopathological correlation in rat model.

作者信息

Kumar Vijay, Kalita Jayantee, Bora Himangsu K, Misra Usha K

机构信息

Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India.

Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India.

出版信息

Regul Toxicol Pharmacol. 2016 Nov;81:372-380. doi: 10.1016/j.yrtph.2016.09.025. Epub 2016 Sep 23.

DOI:10.1016/j.yrtph.2016.09.025
PMID:27670080
Abstract

Excess of copper is toxic to different organs. We aim to study the histopathological changes of liver, kidney, and brain following oral CuSO4 exposure for different duration and doses in rat model. Fifty-four males Wistar rats (205 ± 10 g) were included and divided into control (group-I) and experimental (group-II and III) arms. An oral dose of 100 and 200 mg/kgBWt/Day CuSO4 was given to group-II and III respectively and group-I received normal saline by gavage. Six rats from each group were sacrificed on days 30, 60 and 90 for biochemical and histopathological examinations. The histopathological changes were graded on 1-5 scores and correlated with respective laboratory parameters. The organ functions were worsened in experimental group with increasing dose and time. Histopathological study revealed edema, hemorrhage, necrosis and fibrosis/gliosis in experimental group. The worst histopathological severity score ranged from 4 to 5(median 5) in liver, 3-5(median 4) in kidney and 4-5(median 5) in brain. The edema and hemorrhage were more marked at 30 days and fibrosis/gliosis at 90 days. In conclusion, high-dose Cu toxicity results in structural damage to liver, kidney, and brain that correlates with organ dysfunction, Cu, GSH, TAC, and MDA concentrations. Liver damage is more severe and occurs earlier than other organs.

摘要

过量的铜对不同器官具有毒性。我们旨在研究大鼠模型经口暴露于不同剂量和时长的硫酸铜后肝脏、肾脏和大脑的组织病理学变化。纳入54只雄性Wistar大鼠(体重205±10克),并分为对照组(I组)和实验组(II组和III组)。分别给予II组和III组口服剂量为100和200毫克/千克体重/天的硫酸铜,I组经口给予生理盐水。在第30、60和90天,每组处死6只大鼠进行生化和组织病理学检查。组织病理学变化按1 - 5分进行评分,并与相应的实验室参数相关联。随着剂量增加和时间延长,实验组的器官功能恶化。组织病理学研究显示实验组出现水肿、出血、坏死和纤维化/胶质增生。肝脏的最严重组织病理学严重程度评分为4至5分(中位数为5),肾脏为3至5分(中位数为4),大脑为4至5分(中位数为5)。水肿和出血在第30天更为明显,纤维化/胶质增生在第90天更为明显。总之,高剂量铜毒性导致肝脏、肾脏和大脑的结构损伤,这与器官功能障碍、铜、谷胱甘肽、总抗氧化能力和丙二醛浓度相关。肝脏损伤比其他器官更严重且出现更早。

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