Cadmium induces renal inflammation by activating the NLRP3 inflammasome through ROS/MAPK/NF-κB pathway in vitro and in vivo

• Published in: Archives of toxicology 2021-11, Vol.95 (11), p.3497-3513
• Main Authors: Li, Ziyin, Chi, Huiqin, Zhu, Wei, Yang, Guangyu, Song, Jia, Mo, Lijun, Zhang, Yitian, Deng, Yudi, Xu, Feifei, Yang, Jiani, He, Zhini, Yang, Xingfen
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Acute Kidney Injury - chemically induced; Animals; Biomedical and Life Sciences; Biomedicine; Cadmium; Cadmium - toxicity; Cadmium - urine; Cadmium chloride; Cell Line, Transformed; Damage; Environmental Health; Epithelial cells; Epithelium; Female; Glucosaminidase; Humans; IL-1β; Inflammasomes; Inflammation; Inflammation - etiology; Inflammatory response; Inorganic Compounds; Interleukin 18; Kidney - drug effects; Kidney - pathology; Kidney Tubules, Proximal; Kidneys; Kinases; MAP kinase; Mitogen-Activated Protein Kinase Kinases - metabolism; NF-kappa B - metabolism; NF-κB protein; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Occupational Medicine/Industrial Medicine; Oxidative stress; Pathogenesis; Pharmacology/Toxicology; Pyrin protein; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Serum levels; Signal Transduction; Signaling; Telomerase
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-021-03157-2

Cadmium (Cd) has been reported to induce kidney damage by triggering oxidative stress and inflammation. The NLR family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated a role in the pathogenesis of inflammation. However, the connection between Cd and NLRP3 inflammasome in the development of renal inflammation remains unknown. In this study, in vitro experiments based on the telomerase-immortalized human renal proximal-tubule epithelial cell line (RPTEC/TERT1) were carried out. Results revealed that CdCl 2 (2–8 μM) increased ROS production and activated NLRP3, thereby enhancing secretion of IL-1β and IL-18 ( P