Renoprotective effect of scutellarin on cisplatin-induced renal injury in mice: Impact on inflammation, apoptosis, and autophagy

• Main Authors: Chao-Yue Sun, Juan Nie, Zuo-Liang Zheng, Jie Zhao, Liu-Mei Wu, Ying Zhu, Zu-Qing Su, Guang-Juan Zheng, Bing Feng
• Format: Article
• Language: English
• Published: Elsevier 2019-04-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Scutellarin; Cisplatin; Nephrotoxicity; Inflammation; Apoptosis; Autophagy
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332218381125

Cisplatin remains the standard first-line chemotherapeutic agent in the treatment of many types of cancers, but its clinical application is hindered by its severe nephrotoxicity. Previous studies reported that scutellarin enhanced the anti-cancer activity of cisplatin in lung cancer cells, with no confirmation on cisplatin-induced renal damage. Here, we investigated the nephroprotective effect of scutellarin on cisplatin-induced renal injury and its underlying mechanisms. Renal function, histological change, inflammation, apoptosis, autophagy and involved pathways were investigated. Pretreatment with scutellarin prevented cisplatin-induced decline of renal function including BUN, CRE, and histological damage. Scutellarin also reduced renal inflammation by suppressing the levels of pro-inflammatory cytokine, TNF-α and IL-6. Similarly, scutellarin administration inhibited apoptosis triggered by cisplatin through reducing the expressions of Cleaved caspase-3, Cleaved PARP, p53, and the ratio of Bax/Bcl-2. Moreover, scutellarin prevented cisplatin-induced inhibition of autophagy via enhancing LC3-II/LC3-I and Atg7, and inhibition of p62. Of note, the activations of JNK, ERK, p38 and stat3 induced by cisplatin were strikingly attenuated in scutellarin-treated mice. Thus, these results provide compelling evidence that scutellarin is a novel nephroprotectant against cisplatin-induced renal toxicity.