Danshensu attenuates cisplatin-induced nephrotoxicity through activation of Nrf2 pathway and inhibition of NF-κB

Abstract

The clinical application of cisplatin was mainly limited by severe nephrotoxicity. Danshensu was the main pharmacological active diterpenoids which extracted from the roots of Salvia milthiorriza Bunge. This study is aimed to investigate the protective effects and potential mechanisms of Danshensu against cisplatin-induced nephrotoxicity. After fasting for 12 h, all mice groups except the control group were administered a single intraperitoneal injection of 25 mg/kg cisplatin. 1 h later, cisplatin (25 mg/kg) + Danshensu (15 mg/kg, 30 mg/kg, 60 mg/kg) groups were treated with corresponding doses of Danshensu once a day for 7 consecutive days. Blood urea nitrogen (BUN), creatinine, reactive oxygen species (ROS), superoxide dismutase (SOD), Glutathione peroxidase (GPx), Catalase (CAT) and malondialdehyde (MDA) were assayed in this study. The expression of inflammatory cytokines TNF-α, IL-6 and IL-1β were examined by ELISA. The results showed that Danshensu could improve kidney damage, attenuate serum BUN, creatinine, cytokines and oxidative stress markers. Further studies showed that Danshensu can induce Nrf2/HO-1 activation and inhibition of NF-κB pathway. In conclusion, Danshensu exerts the protective effects on cisplatin-induced nephrotoxicity, which may be related to the activation of Nrf2/HO-1 and inhibition of NF-ĸB pathway.

Keywords: Cisplatin; Danshensu; Inflammation; Nephrotoxicity; Oxidative stress.