Hyperoside attenuates Cd-induced kidney injury via inhibiting NLRP3 inflammasome activation and ROS/MAPK/NF-κB signaling pathway in vivo and in vitro

• Published in: Food and chemical toxicology 2023-02, Vol.172, p.113601-113601, Article 113601
• Main Authors: Li, Ziyin, Liao, Weizuo, Yin, Xinxin, Liu, Lili, Zhao, Zhiqiang, Lu, Xiaodan, Xu, Feifei, Lin, Xiuqin, Chen, Yingsi, Song, Jia, He, Zhini, Wei, Qinzhi, Wu, Weiliang, Wu, Yongning, Yang, Xingfen
• Format: Article
• Language: English
• Subjects: Animals; Cadmium; Cadmium - metabolism; Cadmium - toxicity; Female; Humans; Hyperoside; Inflammasomes - metabolism; Inflammation; Inflammation - metabolism; Kidney; MAPK/NF-κB; Mice; Mice, Inbred C57BL; NF-kappa B - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; Reactive Oxygen Species - metabolism; Signal Transduction
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2023.113601

Cadmium accumulates in the kidney and causes inflammation. The NLRP3 inflammasome has been linked to the pathogenesis of inflammation. Hyperoside (HYP) possesses potent nephroprotective properties against of kidney injury. This study aimed to research the effects and related mechanism of HYP on Cd-induced kidney damage. Wide-type and NLRP3−/− mice were used to determine the role of NLRP3 inflammasome in Cd-induced renal dysfunction. Female C57BL/6 were treated with Cd (50 m,g/L) and HYP (25, 50 mg/kg) for 12 weeks. In vitro experiments, the human renal proximal-tubule epithelial cells (RPTEC/TERT1) were pretreated with HYP (50–200 μM) before exposure to Cd. NLRP3 deficiency attenuated Cd-induced NLRP3 activation, inflammation and kidney injury in mice. HYP treatment significantly alleviated Cd-induced kidney injury by decreasing indexes of kidney function, reducing pro-inflammatory cytokines release, decreasing ROS production and suppressing NLRP3 inflammasome activation. Moreover, treatment with siRNA targeting NLRP3 blocked the anti-inflammatory protective effect of HYP in Cd-treated cells. Additionally, HYP markedly inhibited Cd-induced MAPK/NF-κB pathway stimulation in vitro and in vivo. The findings indicated HYP conferred protection against Cd-induced kidney inflammation via suppression of NLRP3 inflammasome mediated by ROS/MAPK/NF-κB signaling. Our results thus support the notion of developing HYP as promising therapeutic candidate for Cd-induced kidney injury. [Display omitted] •NLRP3 deficiency inhibited Cd-caused inflammation and NLRP3 inflammasome activation in vivo.•Cd induced inflammation through ROS/MAPK/NF-κB pathway and NLRP3 inflammasome.•Hyperoside conferred protection against Cd-induced kidney injury.•Hyperoside inhibited Cd-induced kidney inflammation via suppressing NLRP3 inflammasome and ROS/MAPK/NF-κB signaling.•Hyperoside may be as an antagonist for cadmium toxicity.