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However, it remains unclear whether Cr(VI) perturbs essential trace elements and antioxidant gene expression, triggers apoptosis, or disrupts hepatic lipid metabolism in New Zealand rabbits. Methods: To address this knowledge gap, twenty-four 30-day-old New Zealand rabbits were randomly allocated to one control and three Cr(VI)-treated groups (differing in Cr(VI) concentration) and maintained for 28 days. Livers were then harvested for analysis. Total Cr and essential trace elements were quantified by ICP-OES. Hematoxylin\u2013eosin staining and transmission electron microscopy were employed to assess histopathological and ultrastructural alterations, respectively. Hepatic lipid accumulation was visualized with Oil Red O staining. QRT-PCR was used to determine the expression of antioxidant and lipid-metabolism-related genes. Results: Cr(VI) was detectable in liver tissue at all exposure levels and was accompanied by significant decreases in four essential trace elements (Fe, Mn, Zn, and Se); Cu displayed a biphasic response, rising at lower Cr(VI) doses before declining at higher doses. Histopathological and ultrastructural analyses revealed overt hepatic injury. Notably, all Cr(VI) treatments elevated antioxidant gene expression, indicating activation of hepatic defense pathways. Lipid metabolism was also disrupted, evidenced by increased lipid deposition and up-regulation of genes governing hepatic fat metabolism. Conclusions: Collectively, these findings demonstrate that Cr(VI) elicits dose-dependent activation of hepatic antioxidant defenses, promotes apoptosis, and induces lipid-metabolic disorders in New Zealand rabbit hepatocytes. This study provides novel mechanistic insights into Cr(VI)-induced hepatotoxicity and offers a valuable reference for evaluating the hepatic risks of environmental Cr(VI) exposure in this species.<\/jats:p>","DOI":"10.3390\/metabo15100637","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T15:54:54Z","timestamp":1758642894000},"page":"637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hexavalent Chromium Induces Defense Responses, Hepatocellular Apoptosis, and Lipid Metabolism Alterations in New Zealand Rabbit Livers"],"prefix":"10.3390","volume":"15","author":[{"given":"Junzhao","family":"Yuan","sequence":"first","affiliation":[{"name":"Zhengzhou Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases, College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuqing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory of Unconventional Feed Resources Innovative Utilization, Institute of Livestock Product Quality and Safety Technology Research, Henan University of Animal Husbandry and Economy, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pandeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Ren","sequence":"additional","affiliation":[{"name":"Zhengzhou Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases, College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhen","family":"Song","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s10653-024-02297-5","article-title":"Chromium supplementation and type 2 diabetes mellitus: An extensive systematic review","volume":"46","author":"Georgaki","year":"2024","journal-title":"Env. 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