{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T09:39:35Z","timestamp":1775381975122,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22206059"],"award-info":[{"award-number":["22206059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have previously found that a mixture exposure of 2,2\u2032,4,4\u2032\u2010tetrabromodiphenyl ether (BDE\u201047) and cadmium (Cd) causes kidney damage; however, the mechanism was not fully understood. The aryl hydrocarbon receptor (AhR) is a ligand\u2013receptor transcription factor that plays an important role in the adaptive response or metabolic detoxification of environmental toxins. Thus, this study aimed to examine the role of AhR in kidney toxicity. BDE\u201047 (50\u2009\u03bcM) or Cd (5\u2009\u03bcM) exposure reduced cell viability in renal tubular epithelial cells (HKC), with a larger effect observed in co\u2010treatment. The cell morphology presented pyroptotic changes, including swollen cells, large bubbles, and plasma membrane pore formation. The gene expressions of AhR, heat shock protein 90 (Hsp90), AhR nuclear translocator (ARNT), and cytochrome P450 1B1 (CYP1B1) were increased, while CYP1A1 was decreased. Reactive oxygen species (ROS) were generated, which was reduced by the AhR antagonist CH223191. The apoptosis, necrosis, and intracellular lactated hydrogenase (LDH) release was elevated, and this was attenuated by N\u2010acetylcysteine (NAC). Furthermore, the pyroptosis pathway was activated with increased protein levels of cleaved\u2010caspase\u20103 and gasdermin E N\u2010terminal (GSDME\u2010NT), while caspase\u20108, caspase\u20103, and GSDME were decreased. These effects were alleviated by NAC and CH223191. Our data demonstrate a combined effect of BDE\u201047 and Cd on nephrotoxicity by activating AhR to induce ROS contributing to GSDME\u2010dependent pyroptosis, and retardation of the AhR pathway could reduce this toxicity.<\/jats:p>","DOI":"10.1002\/tox.23957","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T13:04:05Z","timestamp":1694696645000},"page":"289-298","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["2,2\u2032,4,4\u2032\u2010Tetrabromodiphenyl ether and cadmium co\u2010exposure activates aryl hydrocarbon receptor pathway to induce <scp>ROS<\/scp> and <scp>GSDME<\/scp>\u2010dependent pyroptosis in renal tubular epithelial cells"],"prefix":"10.1002","volume":"39","author":[{"given":"Yating","family":"Sheng","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine, Forensic and Pathology Laboratory College of Medicine, Jiaxing University  Jiaxing 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