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抗逆转录病毒药物替诺福韦对Wistar大鼠肝肾功能指标的影响:维生素E的保护作用

Effect of tenofovir, an antiretroviral drug, on hepatic and renal functional indices of Wistar rats: protective role of vitamin E.

作者信息

Adaramoye Oluwatosin Adekunle, Adewumi Olubusuyi Moses, Adesanoye Omolola Abidemi, Faokunla Opeyemi Olubunmi, Farombi Ebenezer Olatunde

机构信息

Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.

出版信息

J Basic Clin Physiol Pharmacol. 2012 Apr 26;23(2):69-75. doi: 10.1515/jbcpp.2011.0042.

Abstract

BACKGROUND

Tenofovir (TFR) is a nucleotide reverse transcriptase inhibitor with activity against human immunodeficiency virus. We studied the effect of TFR administered to Wistar rats on hepatic and renal function markers and the possible modulatory role of vitamin E (Vit E).

METHODS

The study consists of four groups of six rats each. The first group served as control, the second group received TFR at 50 mg/kg/day for 4 weeks, third group received TFR and Vit E, and the last group received Vit E alone.

RESULTS

TFR administration caused a significant (p<0.05) increase in the levels of serum urea, creatinine, urinary glucose, and protein by 65%, 51%, 88%, and 79%, respectively, relative to controls. This was followed by a significant (p<0.05) reduction in creatinine clearance of TFR-treated rats. There were no significant differences (p>0.05) in the activities of serum aminotransferases, γ-glutamyltransferase, and alkaline phosphatase in TRF-treated rats relative to controls. TFR administration caused a marked elevation of malondialdehyde (MDA; index of lipid peroxidation) in the animals. Specifically, serum, hepatic, and renal MDA levels increased by 75%, 90%, and 102%, respectively. TRF-treated rats had significantly (p<0.05) reduced activities of renal catalase, glutathione-S-transferase, and superoxide dismutase. Supplementation of Vit E ameliorated TFR-induced effects by decreasing the levels of MDA and enhancing the activities of renal antioxidative enzymes. The biochemical data were supported by histopathological findings from the slides.

CONCLUSIONS

TFR increased oxidative stress and altered kidney function markers in the rats, whereas supplementation of Vit E attenuated these effects.

摘要

背景

替诺福韦(TFR)是一种核苷酸逆转录酶抑制剂,对人类免疫缺陷病毒具有活性。我们研究了给Wistar大鼠施用替诺福韦对肝肾功能指标的影响以及维生素E(维生素E)可能的调节作用。

方法

该研究由四组组成,每组六只大鼠。第一组作为对照,第二组以50mg/kg/天的剂量接受替诺福韦治疗4周,第三组接受替诺福韦和维生素E,最后一组仅接受维生素E。

结果

与对照组相比,施用替诺福韦导致血清尿素、肌酐、尿糖和蛋白质水平分别显著(p<0.05)升高65%、51%、88%和79%。随后,替诺福韦治疗的大鼠肌酐清除率显著(p<0.05)降低。与对照组相比,替诺福韦治疗的大鼠血清转氨酶、γ-谷氨酰转移酶和碱性磷酸酶的活性没有显著差异(p>0.05)。施用替诺福韦导致动物体内丙二醛(MDA;脂质过氧化指标)显著升高。具体而言,血清、肝脏和肾脏中的MDA水平分别增加了75%、90%和102%。替诺福韦治疗的大鼠肾脏过氧化氢酶、谷胱甘肽-S-转移酶和超氧化物歧化酶的活性显著(p<0.05)降低。补充维生素E通过降低MDA水平和增强肾脏抗氧化酶的活性,改善了替诺福韦诱导的影响。生化数据得到了玻片组织病理学结果的支持。

结论

替诺福韦增加了大鼠的氧化应激并改变了肾功能指标,而补充维生素E减弱了这些影响。

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