Polydatin protects against calcium oxalate crystal-induced renal injury through the cytoplasmic/mitochondrial reactive oxygen species-NLRP3 inflammasome pathway

• Published in: Biomedicine & pharmacotherapy Vol. 167; p. 115621
• Main Authors: Liu, Jiannan, Huang, Jianlin, Gong, Bo, Cheng, Songtao, Liu, Yadong, Chen, Yaodong, Feng, Qiang, Li, Jun, Qiu, Mingxing, Yu, Gui, Liao, Yong
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.11.2023; Elsevier
• Subjects: Cytokines; Inflammation; Kidney; Oxidative stress; Polydatin; Reactive oxygen species; Oxidative stress; Reactive oxygen species; PPI; MDA; Kidney; Cr; ASC; FITC; CaOx; NLRP3; BUN; mtROS; Polydatin; GSDMD; EG; ESWL; Cytokines; TECs; SOD; Inflammation; IL-1β; NAC; IL-18; ROS; HE
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.115621

Oxidative stress and inflammatory responses are critical factors in calcium oxalate (CaOx) crystal-induced renal injury. Reactive oxygen species (ROS) are usually produced in the cytoplasm and mitochondria and trigger the priming and activation of the NLRP3 inflammasome, thereby regulating cytokines and inflammation. Polydatin is a plant rhizome extract with anti-inflammatory, antioxidant, and antitumor effects. However, it remains not clear whether and how these pathophysiological processes exists in CaOx crystal-induced renal inflammatory injury. Here, we measured the expression of the NLRP3 inflammasome, IL-18, IL-1β, intracellular and mitochondrial ROS (mtROS) levels and relevant morphological changes in treated renal tubular epithelial cells (TECs) and stone-forming rats. The study further explored the action of intracellular ROS and mtROS on these inflammatory damage, and the beneficial effects and pathway of polydatin. We verified that CaOx crystal-induced cytoplasmic ROS and mtROS upregulation promoted the priming and activation of the NLRP3 inflammasome, thereby stimulating IL-18/1β maturation and activation. Polydatin can relieve oxidative stress and inflammatory damage by decreasing ROS. We further demonstrated that mtROS is the main target for polydatin to exert the NLRP3 inflammasome-regulating function. The inhibition of mtROS can effectively relieve the inflammatory damage to TECs and kidney caused by CaOx crystal. These findings provide new insight into the relationship between mitochondrial damage and inflammation in nephrolithiasis and show that polydatin-mediated anti-inflammatory and antioxidative protection is a therapeutic strategy for, but not limited to, crystalline nephropathy. [Display omitted] •Oxidative stress and inflammation are closely related in the pathological microenvironment of kidney stones.•mtROS participates in the activation of NLRP3 inflammasome then results in crystal-induced renal injury.•Polydatin protects against inflammatory damage in nephrolithiasis by downregulating mtROS.•Polydatin has a unique advantage in mitochondrial protection as an antioxidant.