Direct exposure with exogenous mitochondria reduce colistin-induced mitochondrial dysfunction and cellular damages in isolated rat renal proximal tubular cells

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. 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 h. 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. 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. To the best of our knowledge, these results provide the first direct experimental evidence that direct exposure with exogenous mitochondria is capable of ameliorating cellular damage following treatment with colistin. These findings support that mitochondrial transplantation may be a promising therapeutic strategy for colistin-associated mitochondrial dysfunction in kidney cells.