Under physiological condition, NF-kB is sequestered in cytoplasm by IkBa subunit, however, on exposure to ROS, sequestration complex breaks down and IkBa is phosphorylated at serine residues by IKKs, allows NF-kB to translocate into the nucleus to promote transcription of inflammatory genes. In the present study, we observed a significant increase in phosphorylated IkBa Benzocaine protein and decrease in intact IkBa protein in cisplatin treated rats when compared to those of vehicle control rats. Fisetin treatment along with cisplatin preserved IkBa degradation, attenuated IkBa phosphorylation and subsequent NF-kB nuclear translocation. A number of studies reported that cisplatin administration caused a significant elevation of IL-6 levels in kidneys. Contrary to this, we did not find any significant change in IL-6 levels in kidney tissues of cisplatin treated rats. Studies have revealed dual role of IL-6 in terms of pro-inflammatory and anti-inflammatory response. Interleukin-6 is known to alleviates reactive oxygen species generation through heme oxygenase-1 induction and BAY 1000394 protecting renal tissues from cisplatin-induced toxicity. At the same time, IL-6 also acts as downstream mediator in TNF-a/NFkB signalling pathway. However, further studies are advocated to confirm this. In physiological conditions, mitochondria continuously generate small quantity of superoxide free radicals by converting 1�C2% of consumed oxygen and act as important source of ROS. Oxidative damage of mitochondria alters the mitochondrial redox function and respiratory chain enzymes, leading to over production of free radicals and cellular dysfunction. Generation of free radicals and mitochondrial oxidative stress-induced dysfunction have been implicated as early events in the pathogenesis of cisplatin-induced nephrotoxicity. It has been reported that endogenous free radical scavengers such as vitamin C and E, glutathione, ubiquinol, superoxide dismutase and glutathione peroxidase protect mitochondria from cisplatin-induced oxidative damage.Recently, Mukhopadhyay et al. demonstrated that a single systemic dose of mitochondrial targeted antioxidants, MitoQ and Mito-CP, that deliver superoxide dismutase mimetics preferentially in to mitochondria, significantly prevented cisplatininduced renal dysfunction in mice.