mitoquinone and Acute-Kidney-Injury

To investigate the effect of mitochondria-targeted antioxidant MitoQ in reducing the severity of renal ischemia-reperfusion injury (IRI) in rats using T. Ischemia-reperfusion injury was induced by temporarily clamping the left renal artery. Rats were pretreated with MitoQ or saline. The MRI examination was performed before and after IRI (days 2, 5, 7, and 14). The T. The standardized signal intensity of the OSOM on IRI kidneys with MitoQ were lower than those with saline on days 5 and 7 (P = 0.004, P < 0.001, respectively). K. These findings demonstrate that MitoQ can reduce the severity of renal damage in rodent IRI models using T

Topics: Acute Kidney Injury; Animals; Contrast Media; Kidney; Magnetic Resonance Imaging; Male; Organophosphorus Compounds; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ubiquinone

Cisplatin is a widely used antineoplastic agent; however, its major limitation is the development of dose-dependent nephrotoxicity whose precise mechanisms are poorly understood. Here we show not only that mitochondrial dysfunction is a feature of cisplatin nephrotoxicity, but also that targeted delivery of superoxide dismutase mimetics to mitochondria largely prevents the renal effects of cisplatin. Cisplatin induced renal oxidative stress, deterioration of mitochondrial structure and function, an intense inflammatory response, histopathological injury, and renal dysfunction. A single systemic dose of mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently prevented cisplatin-induced renal dysfunction. Mito-CP also prevented mitochondrial injury and dysfunction, renal inflammation, and tubular injury and apoptosis. Despite being broadly renoprotective against cisplatin, Mito-CP did not diminish cisplatin's antineoplastic effect in a human bladder cancer cell line. Our results highlight the central role of mitochondrially generated oxidants in the pathogenesis of cisplatin nephrotoxicity. Because similar compounds seem to be safe in humans, mitochondrially targeted antioxidants may represent a novel therapeutic approach against cisplatin nephrotoxicity.

Topics: Acute Kidney Injury; Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Cell Line, Tumor; Cell Survival; Cisplatin; Cyclic N-Oxides; Cytoprotection; Electron Transport Complex IV; Humans; Inflammation; Kidney Tubules; Male; Mice; Mice, Inbred C57BL; Mitochondria; NADH Dehydrogenase; Organophosphorus Compounds; Oxidative Stress; Ubiquinone