The nephroprotective properties of taurine in colistin-treated mice is mediated through the regulation of mitochondrial function and mitigation of oxidative stress

Colistin (COL) belongs to the polymixin class of antibiotics used as the last line antibiotic against drug-resistant infections. However, nephrotoxicity is the major deleterious and dose-limiting side effect associated with COL therapy. Oxidative stress and mitochondrial impairment are suspected mechanisms involved in COL-induced nephrotoxicity. Taurine is one of the most abundant amino acids in the human body with antioxidant and mitochondria protecting properties. The current study was designed to evaluate the potential nephroprotective properties of taurine against COL-associated nephrotoxicity. Mice were treated with COL (15 mg/kg/day, i.v, for 7 consecutive days) alone or in combination with taurine (500 and 1000 mg/kg, i.p). Plasma biomarkers of nephrotoxicity in addition of kidney tissue markers of oxidative stress were evaluated. Additionally, kidney mitochondria were isolated, and several mitochondrial indices were assessed. The COL-associated renal injury was evident by a significant increase in plasma markers of renal injury including creatinine (Cr), and blood urine nitrogen (BUN). COL treatment also caused a significant increase in kidney reactive oxygen species (ROS) and lipid peroxidation (LPO). Renal GSH reservoirs and antioxidant capacity were also decreased in COL-treated animals. Mitochondrial parameters including mitochondrial dehydrogenase activity, membrane potential, GSH, and ATP were significantly decreased while mitochondrial LPO, permeabilization, and GSSG content were increased in the kidney of COL-treated mice. It was found that taurine (500 and 1000 mg/kg, i.p) treatment alleviated COL-induced oxidative stress and mitochondrial dysfunction in the kidney tissue. The data obtained from the current study suggest mitochondrial dysfunction and oxidative stress as fundamental mechanisms of renal injury induced by COL. On the other hand, taurine supplementation protected kidney through decreasing oxidative stress and regulating mitochondrial function.