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Although studies indicate that AFB1 is hepatotoxic, there are few studies on AFB1-induced hepatotoxicity in sheep. Thus, this study examined how AFB1 affected sheep liver function 24 h after the animals received 1 mg\/kg bw of AFB1 orally (dissolved in 20 mL, 4% v\/v ethanol). The acute AFB1 poisoning caused histopathological injuries to the liver and increased total bilirubin (TBIL) and alkaline phosphatase (AKP) levels. AFB1 also markedly elevated the levels of the pro-inflammatory cytokines TNF-\u03b1 and IL-6 while considerably reducing the expression of antioxidation-related genes (SOD-1 and SOD-2) and the anti-inflammatory gene IL-10 in the liver. Additionally, it caused apoptosis by dramatically altering the expression of genes associated with apoptosis including Bax, Caspase-3, and Bcl-2\/Bax. Notably, AFB1 exposure altered the gut microbiota composition, mainly manifested by BF311 spp. and Alistipes spp. abundance, which are associated with liver injury. In conclusion, AFB1 can cause liver injury and liver dysfunction in sheep via oxidative stress, inflammation, apoptosis, and gut-microbiota disturbance.<\/jats:p>","DOI":"10.3390\/toxins14120840","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T04:28:57Z","timestamp":1669868937000},"page":"840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Aflatoxin B1 Exposure in Sheep: Insights into Hepatotoxicity Based on Oxidative Stress, Inflammatory Injury, Apoptosis, and Gut Microbiota Analysis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2953-4068","authenticated-orcid":false,"given":"Yuzhen","family":"Sui","sequence":"first","affiliation":[{"name":"International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lu","sequence":"additional","affiliation":[{"name":"International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoujun","family":"Zuo","sequence":"additional","affiliation":[{"name":"International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidong","family":"Wang","sequence":"additional","affiliation":[{"name":"International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokun","family":"Bian","sequence":"additional","affiliation":[{"name":"International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guizhen","family":"Chen","sequence":"additional","affiliation":[{"name":"International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-8616","authenticated-orcid":false,"given":"Shucheng","family":"Huang","sequence":"additional","affiliation":[{"name":"International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Dai","sequence":"additional","affiliation":[{"name":"International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiju","family":"Dong","sequence":"additional","affiliation":[{"name":"International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2103677","DOI":"10.1002\/smll.202103677","article-title":"Label-Free Mycotoxin Raman Identification by High-Performing Plasmonic Vertical Carbon Nanostructures","volume":"17","author":"Shvalya","year":"2021","journal-title":"Small"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"536","DOI":"10.4315\/0362-028X-57.6.536","article-title":"Methods for Detection and Quantitation of Fumonisins in Corn, Cereal Products and Animal Excreta","volume":"57","author":"Rice","year":"1994","journal-title":"J. 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