{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:59:45Z","timestamp":1785495585051,"version":"3.56.0"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"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","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":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Environmental pollution is complex, and co\u2010exposure can accurately reflect the true environmental conditions that are important for assessment of human health. Cadmium (Cd) is a widespread toxicant that can cause acute kidney injury (AKI), while its combined effect with 2,2\u2032,4,4\u2032\u2010tetrabromodiphenyl ether (BDE\u201047) is not fully understood. Thus, we used an in vivo model where C57BL\/6J mice were treated with low dietary intake of Cd (5\u2009mg\/kg\/day) and\/or BDE\u201047 (1\u2009mg\/kg\/day) for 28\u2009days to examine AKI, and in vitro experiments to investigate the possible mechanism. Results showed that Cd or BDE\u201047 caused pathological kidney damage, accompanied by elevated urea nitrogen (BUN) and urinary creatinine, as well as increased interleukin\u20101\u03b2 (IL\u20101\u03b2) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), and reduced IL\u201010 in kidney tissues. In vitro Cd or BDE\u201047 exposure decreased cell viability and induced cell swelling and blebbing of human embryonic kidney 293 (HEK\u2010293) and renal tubular epithelial cell lines (HKCs), and changes in co\u2010exposure was larger than that in Cd and BDE\u201047 treatment. Oxidative stress indicators of the reactive oxygen species (ROS) and malondialdehyde (MDA) were elevated, while the antioxidant superoxide dismutase (SOD) was decreased. Necrosis occurred with increased lactate dehydrogenase (LDH) release and propidium iodide (PI) staining, which was attenuated by the ROS scavenger N\u2010acetyl\u2010L\u2010cysteine (NAC). Furthermore, necroptotic genes of receptor\u2010interacting protein kinase\u20103 (RIPK3), classical mixed lineage kinase domain\u2010like protein\u2010dependent (MLKL), IL\u20101\u03b2 and TNF\u2010\u03b1 were up\u2010regulated, whereas RIPK1 was down\u2010regulated, which was attenuated by the RIPK3 inhibitor GSK872. These findings demonstrate that Cd or BDE\u201047 alone produces kidney toxicities, and co\u2010exposure poses an additive effect, resulting in AKI via inducing oxidative stress and regulating RIPK3\u2010dependent necroptosis, which offers a further mechanistic understanding for kidney damage, and the combined effect of environmental pollutants should be noticed.<\/jats:p>","DOI":"10.1002\/tox.23869","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T03:39:48Z","timestamp":1687750788000},"page":"2332-2343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cadmium (Cd) and 2,2\u2032,4,4\u2032\u2010tetrabromodiphenyl ether (\n                    <scp>BDE<\/scp>\n                    \u201047) co\u2010exposure induces acute kidney injury through oxidative stress and\n                    <scp>RIPK3<\/scp>\n                    \u2010dependent necroptosis"],"prefix":"10.1002","volume":"38","author":[{"given":"Jie","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Pathology, Jiaxing key laboratory of infectious diseases and bacterial resistance research, Jiaxing Hospital of Traditional Chinese Medicine Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nenghua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Jiaxing key laboratory of infectious diseases and bacterial resistance research, Jiaxing Hospital of Traditional Chinese Medicine Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shipiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Forensic and Pathology Laboratory, Institute of Forensic Science, College of Medicine Jiaxing University  Jiaxing 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