直接作用抗病毒药物调节年轻雌性大鼠不同组织中的线粒体生物发生。

Direct-Acting Antiviral Drug Modulates the Mitochondrial Biogenesis in Different Tissues of Young Female Rats.

机构信息

Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt.

Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19111, Jordan.

出版信息

Int J Mol Sci. 2023 Oct 31;24(21):15844. doi: 10.3390/ijms242115844.

DOI:10.3390/ijms242115844

PMID:37958828

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10647297/

Abstract

(1) Background: Hepatitis C virus (HCV) infection is endemic in Egypt, with the highest prevalence rate worldwide. Sofosbuvir (SOF) is a nucleos(t)ide analog that specifically inhibits HCV replication. This study aimed to explore the possible effects of the therapeutic dose of SOF on the mitochondrial biogenesis and functions of the liver, muscle, and ovarian tissues of young normal female rats. (2) Methods: This study was conducted on 20 female Wistar rats, classified into two groups, the control group and the exposed group; the latter was orally supplemented with 4 mg/kg/day of SOF for 3 months. (3) Results: The exposure to SOF impairs mitochondrial biogenesis via mitochondrial DNA copy number decline and suppressed mitochondrial biogenesis-regulated parameters at mRNA and protein levels. Also, SOF suppresses the DNA polymerase γ (POLG) expression, citrate synthase activity, and mitochondrial NADH dehydrogenase subunit-5 (ND5) content, which impairs mitochondrial functions. SOF increased lipid peroxidation and oxidative DNA damage markers and decreased tissue expression of nuclear factor erythroid 2-related factor 2 (Nfe2l2). (4) Conclusions: The present findings demonstrate the adverse effects of SOF on mitochondrial biogenesis and function in different tissues of young female rats, which mostly appeared in ovarian tissues.

摘要

(1) 背景：丙型肝炎病毒（HCV）感染在埃及流行，全球发病率最高。索磷布韦（SOF）是一种核苷酸类似物，特异性抑制 HCV 复制。本研究旨在探讨 SOF 的治疗剂量对年轻正常雌性大鼠肝脏、肌肉和卵巢组织中线粒体生物发生和功能的可能影响。(2) 方法：本研究共纳入 20 只雌性 Wistar 大鼠，分为对照组和暴露组；后者经口补充 4mg/kg/天 SOF，共 3 个月。(3) 结果：SOF 暴露通过线粒体 DNA 拷贝数下降和 mRNA 及蛋白水平上受调控的线粒体生物发生参数下调来损害线粒体生物发生。此外，SOF 还抑制 DNA 聚合酶γ（POLG）表达、柠檬酸合酶活性和线粒体 NADH 脱氢酶亚单位-5（ND5）含量，从而损害线粒体功能。SOF 增加了脂质过氧化和氧化 DNA 损伤标志物的水平，并降低了核因子红细胞 2 相关因子 2（Nfe2l2）在组织中的表达。(4) 结论：本研究结果表明 SOF 对年轻雌性大鼠不同组织中线粒体生物发生和功能具有不良影响，其中在卵巢组织中最为明显。