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线粒体移植减轻了法维拉韦对大鼠肾近端肾小管细胞的毒性。

Mitochondrial transplantation attenuates toxicity in rat renal proximal tubular cells caused by Favipiravir.

机构信息

Department of Occupational Health and Safety Engineering, School of Health, Alborz University of Medical Sciences, Karaj, Iran.

Research Center for Health, Safety and Environment, Alborz University of Medical Sciences, Karaj, Iran.

出版信息

J Pharm Pharmacol. 2023 Nov 23;75(11):1458-1466. doi: 10.1093/jpp/rgad079.

DOI:10.1093/jpp/rgad079
PMID:37738481
Abstract

OBJECTIVES

Exogenous mitochondria transplantation or mitotherapy can be used to swap out unhealthy mitochondria for functioning ones. Treatment of mitochondrial diseases using this approach may be beneficial.

METHODS

In this study, we looked at the effect of transplanting newly isolated mitochondria on the toxicity that favipiravir (FAV) causes in renal proximal tubular cells (RPTCs). In this study, parameters such as lactate dehydrogenase (LDH) leakiness, reactive oxygen species (ROSs) production, damage to the lysosome membrane, reduced glutathione (GSH) content, extracellular oxidized glutathione (GSSG) content, GSH/GSSG ratio, ATP level, mitochondrial membrane potential (MMP) collapse, Bcl-2 content, and caspase-3 activity were used to assess the protective effects of mitochondrial transplantation against FAV-induced mitochondrial toxicity.

KEY FINDINGS

The statistical analysis showed that the cytotoxicity, ROS production, MMP collapse, lysosomal damage, GSSG levels, and caspase-3 activity brought on by FAV in RPTCs were reduced by transplanting the healthy mitochondria. In addition, it led to an increase in ATP level, GSH content, Bcl-2 content, and GSH/GSSG ratio in RPTCs.

CONCLUSIONS

A recent study found that mitochondrial transplantation is a powerful therapeutic approach for treating nephrotoxicity brought on by xenobiotics.

摘要

目的

外源性线粒体移植或粒体治疗可用于置换不健康的线粒体,为功能正常的线粒体。使用这种方法治疗线粒体疾病可能是有益的。

方法

在本研究中,我们观察了新分离的线粒体移植对肾近端小管细胞(RPTC)中金刚烷胺(FAV)引起的毒性的影响。在本研究中,我们使用乳酸脱氢酶(LDH)渗漏、活性氧(ROS)产生、溶酶体膜损伤、还原型谷胱甘肽(GSH)含量、细胞外氧化型谷胱甘肽(GSSG)含量、GSH/GSSG 比值、ATP 水平、线粒体膜电位(MMP)崩溃、Bcl-2 含量和半胱天冬酶-3 活性等参数来评估线粒体移植对 FAV 诱导的线粒体毒性的保护作用。

主要发现

统计分析表明,移植健康线粒体可减轻 FAV 在 RPTC 中引起的细胞毒性、ROS 产生、MMP 崩溃、溶酶体损伤、GSSG 水平和半胱天冬酶-3 活性。此外,它还导致 RPTC 中 ATP 水平、GSH 含量、Bcl-2 含量和 GSH/GSSG 比值升高。

结论

最近的一项研究发现,线粒体移植是治疗外源性毒物引起的肾毒性的一种有效治疗方法。

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