Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS

• DOI: 10.1016/j.heliyon.2023.e21231
• Publication Date: 2023-11-02T21:10:46Z
• Authors: Tingni Wu; Wenxian Ma; Weili Lu; Zhuofan Huangshen; Shiqing Chen; Qin Yang; Chao Li; Zeng Li; Ning Li; Xiaowen Feng; Li Li; Yu Miao; Jianan Wang; Xueqi Liu; Yuting Cai; Yuan He; Xiaoyan He; Jun Li; Ren Zhao; Jiagen Wen
• Keywords: NOX4

Cisplatin is a chemotherapeutant widely used in treating solid tumors, with the common side effect of acute kidney injury (AKI). Developing effective useful agent for preventing or cisplatin-induced AKI great importance. In this study, we investigate protective vaccarin, chemical entity flavonoid glycoside, against AKI. Cisplatin-treated C57BL/6J mice and human kidney-2 (HK-2) cells were as model The levels blood urea nitrogen (BUN) creatine (Cr) periodic acid-Schiff staining (PAS) scores decreased when vaccarin was administrated. Vaccarin had no impact on renal platinum accumulation, which detected by ICP-MS 6 h after cisplatin injection. Moreover, can significantly alleviate product reactive oxygen species expression nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) AKI, both vivo vitro. addition, receptor-interacting protein kinase 1 (RIPK1) related programmed necrosis (necroptosis), cell apoptosis (shown cleaved-caspase3 flow cytometry) inflammation NLRP3, p-P65 mRNA several inflammatory factors). NOX4 inhibitor GLX351322 (GLX) kowndown siRNA have equivalent When administered together GLX siRNA, did not further increase, indicating index oxidative stress, viability, necroptosis apoptosis. conclusion, via inhibiting NOX4.