The effect of dysfunctional mitochondria in several cell pathologies has been reported in renal diseases, including diabetic nephropathy and acute kidney injury. Previous studies have reported that mitochondrial transplantation provided surprising results in myocardial and liver ischemia, as well as in Parkinson's disease. We aimed to investigate the beneficial effects of isolated mitochondria transplantation from mesenchymal stem cells (MSCs) in vivo, to mitigate renal damage that arises from doxorubicin‐mediated nephrotoxicity and its action mechanism. In this study, a kidney model of doxorubicin‐mediated nephrotoxicity was used and isolated mitochondria from MSCs were transferred to the renal cortex of rats. The findings showed that the rate of isolated mitochondria from MSCs maintains sufficient membrane integrity, and was associated with a beneficial renal therapeutic effect. Following doxorubicin‐mediated renal injury, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for five days. This study found that mitochondrial transplantation decreased cellular oxidative stress and promoted regeneration of tubular cells after renal injury (P < .001, P = .009). Moreover, mitochondrial transplantation reduced protein accumulation of tubular cells and reversed renal deficits (P = .01, P < .001). Mitochondrial transplantation increased Bcl‐2 levels, and caspase‐3 levels decreased in injured renal cells (P < .015, P < .001). Our results provide a direct link between mitochondria dysfunction and doxorubicin‐mediated nephrotoxicity and suggest a therapeutic effect of transferring isolated mitochondria obtained from MSCs against renal injury. To our knowledge, this study is the first study in the literature that showed good therapeutic effects of mitochondrial transplantation in a nephrotoxicity model, which is under‐researched.

中文翻译：

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间充质干细胞线粒体移植对阿霉素介导的大鼠肾毒性的影响。

线粒体功能异常在几种细胞病理学中的作用在肾脏疾病中已有报道，包括糖尿病性肾病和急性肾损伤。先前的研究报道线粒体移植在心肌和肝脏缺血以及帕金森氏病中提供了令人惊讶的结果。我们旨在研究体内从间充质干细胞（MSCs）分离线粒体移植的有益效果，以减轻由阿霉素介导的肾毒性及其作用机制引起的肾脏损害。在这项研究中，使用了由阿霉素介导的肾毒性的肾脏模型，并将来自MSC的线粒体转移到了大鼠的肾皮质。研究结果表明，从MSC中分离出的线粒体的速率保持了足够的膜完整性，并且与有益的肾脏治疗作用有关。阿霉素介导的肾损伤后，将隔离的线粒体或媒介物注入肾皮质，并监测大鼠五天。这项研究发现，线粒体移植可降低肾损伤后细胞的氧化应激并促进肾小管细胞的再生（P  <.001，P  = .009）。此外，线粒体移植减少了肾小管细胞的蛋白质积累并逆转了肾功能不全（P  = .01，P  <.001）。线粒体移植在受损的肾细胞中增加了Bcl-2的水平，并降低了caspase-3的水平（P  <.015，P  <.001）。我们的结果提供了线粒体功能障碍与阿霉素介导的肾毒性之间的直接联系，并提出了转移自MSCs获得的分离的线粒体对肾损伤的治疗作用。据我们所知，该研究是文献中首次在肾毒性模型中显示线粒体移植具有良好的治疗效果的研究，该研究仍在研究中。