Dose-dependent nephrotoxicity limits the therapeutic use of cisplatin in tumor chemotherapy. Natural compounds show a protective effect against cisplatin-induced nephrotoxicity. Rhoifolin is a flavone glycoside that demonstrates antioxidant and antiproliferative effects. The influence and mechanism of rhoifolin on cisplatin-induced nephrotoxicity were investigated in this study. First, a rat model of cisplatin-induced nephrotoxicity was established. Intraperitoneal administration of cisplatin induced renal damage in rats as demonstrated by a decrease in body weight, increase in blood urea, nitrogen and creatinine, and destruction of histological integrity. However, treatment with rhoifolin attenuated cisplatin-induced nephrotoxicity. Second, cisplatin induced oxidative stress and inflammatory response in rats as demonstrated by a decrease in superoxide dismutase, glutathione, glutathione S-transferase and catalase, and an increase in malondialdehyde, tumor necrosis factor-α, and interleukin-6. Also, the administration of rhoifolin led to alleviation of cisplatin-induced oxidative stress and inflammatory response. Finally, cisplatin activated the nuclear factor-kappa B signaling pathway via degradation and phosphorylation of IκBα (inhibitor of kappa B). Administration of rhoifolin inhibited nuclear translocation of NF-κB via down-regulation of phospho-IκBα and phospho-p65, as well as up-regulation of IκBα. In conclusion, the administration of rhoifolin attenuated cisplatin-induced renal damage, oxidative stress and inflammatory response through inhibition of the NF-κB signaling pathway, suggesting a potential adjunct candidate for cisplatin in tumor treatment.
Simvastatin Improves Cardiac Hypertrophy in Diabetic Rats by Attenuation of Oxidative Stress and Inflammation Induced by Calpain-1-Mediated Activation of Nuclear Factor-κB (NF-κB)