Decrease in the percentage of mitochondrial cross-sectional area/cytoplasmic area. Several studies have demonstrated a positive correlation between oxidative stress and apoptosis in experimentally-induced nephrotoxicity. The elevation of caspase-3 activity, in the present study, reveals apoptosis and mitochondrial damage. Cisplatin-induced apoptosis in renal epithelial cells has been previously elucidated and is generally considered to be associated with caspase-3 activation which is the principal executioner caspase in renal tubular apoptosis. Tempol pretreatment succeeded to alleviate the changes induced by the state of oxidative stress in both mitochondrial and postmitochondrial fractions in addition to amelioration of disruption of mitochondrial function and caspase-3 elevation. Several studies have previously demonstrated the role of antioxidants in prevention of cisplatin-induced nephrotoxicity. Tempol has catalase and superoxide dismutase activities which can catalyze the removal of superoxide anions, limit hydroxyl radical formation from H2O2 and accept an electron to form the antioxidant hydroxylamine. The antioxidant activities of tempol have been previously demonstrated experimentally in gentamicin and WZ8040 vancomycin-induced nephrotoxicity. Moreover, tempol has been previously shown to reduce renal cell damage caused by paraquat through its ROS scavenging activities. Several molecular mechanisms for the antioxidant activity of tempol and other nitroxide derivatives have been proposed by inhibition of the iron-driven Fenton reaction with H2O2 by oxidizing transition metal ions, such as iron. Moreover, a direct superoxide anion scavenging activity of nitroxides has been reported. Tempol, a membrane-permeable antioxidant, through its superoxide anion scavenging activity could prevent the increase in mitochondrial superoxide and H2O2 production and preserve the mitochondrial antioxidant enzyme activities including MnSOD and catalase. This was correlated with preservation of mitochondrial respiratory function and prevention of mitochondria-induced apoptosis as indicated by normalization of caspase-3 activity and histological examinations of renal tubules and mitochondria. Tempol treatment has previously restored mitochondrial membrane potential and reduced tissue oxidative damage in Atm-deficient mice, both in vitro and in vivo. In addition, tempol protected rat proximal tubular cells against H2O2-induced cellular injury and death in a previous in vitro study. In conclusion, the present study highlights the potential role of tempol in alleviating cisplatin-induced mitochondrial dysfunction without affecting its antitumor activity via reducing ROS formation, protecting electron transport complexes, favoring energy production and inhibiting apoptosis in addition to improving histological changes. The beneficial effect of tempol in cisplatin-induced nephrotoxicity is an important outcome which needs to be evaluated in clinical studies. Epithelial cells in the lung act as the front line of defense against various infectious and noxious substances inhaled from the air. Specifically, the epithelium of the respiratory tract is subject to various chemical, physical, environmental and inflammatory insults.