The effects of mesenchymal stem cell mitochondrial transplantation on doxorubicin‐mediated nephrotoxicity in rats

Journal of Biochemical and Molecular Toxicology - Tập 35 Số 1 - 2021
Gökhan Burçin Kubat1,2, Mehmet Özler3, Oner Ulger3, Özgür Ekinci4, Özbeyen Atalay5, Ertuğrul Çelik1, Mükerrem Safalı1, Murat T. Budak5
1Department of Pathology, Gulhane Training and Research Hospital, Health Sciences University, Ankara, Turkey
2Department of Sport Sciences and Technology Hacettepe University Ankara Turkey
3Department of Physiology, Health Sciences University, Ankara, Turkey
4Department of Pathology, Gazi University, Ankara, Turkey
5Department of Physiology, Hacettepe University, Ankara, Turkey

Tóm tắt

AbstractThe 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.

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Journal of Biochemical and Molecular Toxicology

Tập 35 Số 1

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