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Pyroptosis is a special mode of inflammation and programmed cell death involved in the activation of inflammasome and Caspase\u20101 and the release of inflammatory cytokines. This study aims to confirm whether H<jats:sub>2<\/jats:sub>S can alleviate U\u2010induced rat NRK\u201052<jats:sup>E<\/jats:sup> cell pyroptosis and to investigate the H<jats:sub>2<\/jats:sub>S underlying regulatory mechanism. Our results indicate that pretreatment with NaHS (an H<jats:sub>2<\/jats:sub>S donor) significantly inhibited U\u2010increased reactive oxygen species level, NLRP3, apoptosis\u2010related speck\u2010like protein consisting of a caspase recruitment domain (ASC), and cleaved Caspase\u20101 proteins expression, gasdermin D\u00a0messenger\u00a0RNA\u00a0(GSDMD mRNA) expression, interleukin (IL)\u22121\u03b2 and IL\u201018 contents, lactate dehydrogenase leakage, and numbers of double\u2010positive dying kidney cells. NaHS application evidently augmented phosphorylated PI3K, AKT, and mTOR expression as well as ratios of their respective phosphorylation to the corresponding total proteins which were downregulated by U treatment. But, LY294002 (a PI3K inhibitor) administration effectively abrogated the consequences of NaHS on the levels of p\u2010PI3K, cleaved Caspase\u20101, ASC and NLRP3 proteins, GSDMD mRNA\u00a0expression, and\u00a0(IL)\u20101\u03b2\u00a0and IL\u201018 contents. Simultaneously, LY294002 significantly reversed the effects of NaHS on U\u2010induced pyroptosis rate and cytotoxicity. Taken together, these results indicate that H<jats:sub>2<\/jats:sub>S ameliorated U\u2010triggered NRK\u201052<jats:sup>E<\/jats:sup> cells pyroptosis via upregulation of PI3K\/AKT\/mTOR pathway, suggesting a novel role for H<jats:sub>2<\/jats:sub>S in the management of nephrotoxicity caused by U exposure.<\/jats:p>","DOI":"10.1002\/jbt.23220","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T11:34:30Z","timestamp":1662982470000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Hydrogen sulfide attenuates uranium\u2010induced kidney cells pyroptosis via upregulation of PI3K\/AKT\/mTOR signaling"],"prefix":"10.1002","volume":"37","author":[{"given":"Qiaoni","family":"Hu","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Tumor Immunology and Microenvironment Regulation, Faculty of Basic Medical Sciences Guilin Medical University Guilin city Guangxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Tumor Immunology and Microenvironment Regulation, Faculty of Basic Medical Sciences Guilin Medical University Guilin city Guangxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1756-6484","authenticated-orcid":false,"given":"Jifang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Tumor Immunology and Microenvironment Regulation, Faculty of Basic Medical Sciences Guilin Medical University Guilin city Guangxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghui","family":"Song","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Tumor Immunology and Microenvironment Regulation, Faculty of Basic Medical Sciences Guilin Medical University Guilin city Guangxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaohao","family":"Gu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Tumor Immunology and Microenvironment Regulation, Faculty of Basic Medical Sciences Guilin Medical University Guilin city Guangxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Li","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Tumor Immunology and Microenvironment Regulation, Faculty of Basic Medical Sciences Guilin Medical University Guilin city Guangxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2017.04.032"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-020-02676-8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2009.0028"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2009.10.009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2007.00447.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2021.0014"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2017.12.005"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S275595"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.118.112268"},{"key":"e_1_2_8_11_1","first-page":"170","volume":"8","author":"Feng Y. 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