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To ascertain the relationship between the protective mechanism of Se against Cd nephrotoxicity and ferroptosis and pyroptosis, we randomly divided 48 sheep into four groups and treated them with Cd chloride and\/or sodium selenite for 50\u2009days. The data confirmed that Cd apparently resulted in impaired kidney histology and function, depletion of GSH and nicotinamide adenine dinucleotide phosphate contents and CAT and SOD activities, elevation of MDA level, as well as the reduction in selenoprotein mRNA (GPX1, GPX4, TXNRD1, SELP) levels and GPX4 protein level and immunofluorescence intensity. Meanwhile, Cd induced ferroptosis by causing iron overload, up\u2010regulating PTGS2, NCOA4, TFR1, and LC3B mRNA levels and PTGS2 and LC3B\u2010II\/LC3B\u2010I protein levels, reducing SLC7A11 and FTH1 mRNA and protein levels, and enhancing the immunofluorescence co\u2010localization of FTH1\/LC3B. Moreover, it was also found that Cd triggered pyroptosis, which was evidenced by the increase of NLRP3 immunohistochemical positive signal, GSDMD\u2010N immunofluorescence intensity, IL\u20101\u03b2 and IL\u201018 release and the levels of pyroptosis\u2010related mRNA (NLRP3, ASC, Caspase\u20101, GSDMD, IL\u20101\u03b2 and IL\u201018) and proteins (NLRP3, Caspase\u20101p20, GSDMD\u2010N, IL\u20101\u03b2 and IL\u201018). Notably, Se increased the expression level of GPX4 and the transcription factors TFAP2c and SP1, and ameliorated Cd\u2010induced changes in aforementioned factors. In conclusion, GPX4 utilization by Se might be required to alleviate Cd\u2010induced ferroptosis and pyroptosis in sheep kidney.<\/jats:p>","DOI":"10.1002\/tox.23740","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T06:29:04Z","timestamp":1674109744000},"page":"962-974","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["<scp>GPX4<\/scp>\n                    utilization by selenium is required to alleviate cadmium\u2010induced ferroptosis and pyroptosis in sheep kidney"],"prefix":"10.1002","volume":"38","author":[{"given":"Li","family":"Wang","sequence":"first","affiliation":[{"name":"Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology Jiangxi Agricultural University  Nanchang Jiangxi 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