{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:48:34Z","timestamp":1793285314430,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Talent Introduction Project of Anhui Science and Technology University","award":["DKYJ202302"],"award-info":[{"award-number":["DKYJ202302"]}]},{"name":"Veterinary Science Peak Discipline Project of Anhui Science and Technology University","award":["XK-XJGF002"],"award-info":[{"award-number":["XK-XJGF002"]}]},{"name":"Major projects supported by Department of Education Anhui Province","award":["2023AH040282"],"award-info":[{"award-number":["2023AH040282"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>As the global average temperature increases, heat stress (HS) caused by high temperatures has become a key constraint to the development of the poultry industry. As the primary metabolic organ, HS can induce liver injury in chickens, thereby compromising feed safety. However, the precise mechanisms underlying HS-induced liver injury remain to be elucidated. The objective of this study is to explore the impact of HS on liver damage, oxidative stress, the Keap1-Nrf2 pathway, ferroptosis and cuproptosis in chickens. A total of 70 chickens were selected for this experiment and divided into a CON group and a HS group: the CON group was reared in a normal-temperature environment (24 \u00b1 1\u00b0C), whilst the chronic HS group was reared in a high-temperature environment (33 \u00b1 1\u00b0C). The findings of the study suggested that HS has the potential to induce liver dysfunction, oxidative stress, and disruption of the Keap1-Nrf2 pathway. HS has been demonstrated to induce Fe2+ accumulation in chicken livers, inhibit the expression of FTH1, FSP1, SLC7A11 and Gpx4, and simultaneously upregulate the expression of CD71, PTGS2 and ACSL4, thereby promoting ferroptosis. Furthermore, Cu2+ accumulation in the liver upregulates HSP70, DLAT and Lip-DLAT levels and downregulates the expression of ATP7B, PDH1A, PDHB, PDK4, DLST and FDX1, thereby inducing cuproptosis. Subsequent correlation analysis revealed that HS can induce ferroptosis and cuproptosis via the HO-1\/FDX1\/Gpx4 pathway. This finding provides new insights into the mechanisms underlying HS-induced liver injury.<\/jats:p>","DOI":"10.3390\/vetsci13060512","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:16:08Z","timestamp":1779783368000},"page":"512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Heat Stress in the Liver of Chicken: Insights from Keap1-Nrf2 Pathway Mediated Ferroptosis and Cuproptosis via the HO-1\/FDX1\/Gpx4 Axis"],"prefix":"10.3390","volume":"13","author":[{"given":"Guangqing","family":"Xu","sequence":"first","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8300-4158","authenticated-orcid":false,"given":"Deqiang","family":"Yan","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zekai","family":"Wang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxue","family":"Ding","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Xiong","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojun","family":"He","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyang","family":"Ma","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40104-025-01283-w","article-title":"Thermal stress responses and heat stress resilience genes in chickens are revealed through genomic and transcriptomic insights","volume":"17","author":"Hossain","year":"2026","journal-title":"J. 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