{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:37:28Z","timestamp":1785411448895,"version":"3.56.0"},"reference-count":85,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Initial Scientific Research Foundation of Doctoral in Henan University of Animal Husbandry and Economy","award":["906\/M4050208"],"award-info":[{"award-number":["906\/M4050208"]}]},{"award":["906\/M4050208"],"award-info":[{"award-number":["906\/M4050208"]}],"id":[{"id":"https:\/\/ror.org\/003xyzq10","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Henan University of Animal Husbandry and Economy"},{"id":[{"id":"https:\/\/ror.org\/003xyzq10","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Project of Science and Technology of Henan Province","award":["2521021111015"],"award-info":[{"award-number":["2521021111015"]}]},{"name":"Department of Science and Technology of Henan Province"},{"name":"the Key Projects of Henan Province Colleges and Universities","award":["24A230009"],"award-info":[{"award-number":["24A230009"]}]},{"DOI":"10.13039\/501100009101","name":"Henan Provincial Department of Education","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009101","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Hexavalent chromium (Cr(VI)) is a widespread environmental toxic heavy metal with strong oxidative properties; however, its immunotoxicity and metabolic mechanisms in rabbit spleen remain largely unclear. Methods: In this study, New Zealand rabbits were exposed to 0, 12.5, 25, and 50 mg\/L Cr(VI) (as potassium dichromate, K2Cr2O7) via drinking water for four weeks to investigate splenic damage and the underlying molecular pathways. Spleen pathological injury was evaluated by hematoxylin and eosin (H&amp;E) staining, and the distribution of T cells, B cells, and macrophages was assessed by immunohistochemistry. Antioxidant enzyme activities and antioxidant substance levels were determined using ELISA, and the relative mRNA expression of immune factor genes, antioxidant-related genes, and ferroptosis-related genes was quantified by quantitative real-time PCR (qRT-PCR). In addition, the distribution of iron in splenic tissue was detected by enhanced Prussian blue staining. Results: Our results demonstrate that high-dose Cr(VI) significantly inhibited body weight gain, induced lymphocyte atrophy, vacuolization, and widening of intercellular spaces in the splenic white pulp. Furthermore, Cr(VI) reduced T and B lymphocyte populations, promoted macrophage infiltration and inflammatory cytokine gene expression in a concentration-dependent manner, impaired total antioxidant capacity, and led to a decrease in glutathione (GSH) levels in the spleen. Additionally, Cr(VI) exposure increased iron accumulation, activated the ACSL4\u2013NOX lipid peroxidation cascade, and downregulated GPX4 expression, ultimately triggering ferroptosis. Conclusions: These findings reveal that Cr(VI) causes splenic immune injury by disrupting oxidative homeostasis and inducing ferroptosis, providing novel insights for evaluating immunotoxicity and identifying metabolic targets under Cr(VI) pollution.<\/jats:p>","DOI":"10.3390\/metabo16060430","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:04:04Z","timestamp":1781874244000},"page":"430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Mechanisms of Hexavalent Chromium-Induced Splenic Immune Injury via Oxidative Stress and Ferroptosis Pathways in New Zealand Rabbits"],"prefix":"10.3390","volume":"16","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 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxing","family":"Song","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangxing","family":"Jin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450046, 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 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.chemosphere.2018.12.105","article-title":"Chromium and fluoride contamination in groundwater around leather tanning industries in southern India: Implications from stable isotopic ratio \u03b4(53)Cr\/\u03b4(52)Cr, geochemical and geostatistical modelling","volume":"220","author":"Kanagaraj","year":"2019","journal-title":"Chemosphere"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/10408440701845401","article-title":"Trivalent chromium: Assessing the genotoxic risk of an essential trace element and widely used human and animal nutritional supplement","volume":"38","author":"Eastmond","year":"2008","journal-title":"Crit. 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