Transplantation of Healthy Mitochondria into Rat Renal Proximal Tubular Cells Reduces Colistin- Induced Mitochondrial Dysfunction and Cellular Damage: An In Vitro Study

Abstract

Abstract Background Kidney damage caused by colistin (polymyxin E) can bring about a decrease in creatinine clearance, potential proteinuria, cylindruria and oliguria in treated patients. It is therefore imperative to develop a new therapeutic strategy for reducing kidney damage after treatment with colistin. Mitochondrial damage is one of contributing factors in colistin-induced nephrotoxicity. Given the therapeutic benefits of mitochondrial transplantation by exogenous healthy mitochondria, we hypothesized that this strategy would be capable of ameliorating renal proximal tubular cells damage following exposure with colistin.Methods For this purpose, we isolated rat renal proximal tubular cells (RPTCs) form kidney and exposed them with toxic concertation of colistin with/without rat healthy isolated mitochondria for 4 hours. Cellular parameters such as lactate dehydrogenase (LDH), reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP), caspase 3 activation, lysosomal damage, glutathione and ATP content were measured.Results The results showed that administration of isolated mitochondria could improve colistin-induced nephrotoxicity and reduce mitochondrial dysfunction. Exogenous mitochondria reduced the activity of LDH, production of ROS, ATP and GSH depletion, loss of MMP, lysosomal damages and cell death.Conclusion To the best of our knowledge, these results provide the first direct experimental evidence that mitochondrial transplantation is capable of ameliorating cellular damage following treatment with colistin. These findings support that mitochondrial transplantation can be a promising therapeutic strategy for colistin-associated mitochondrial dysfunction and kidney damage.