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However, it remains unknown whether long\u2010term exposure to xylazine causes nonalcoholic fatty liver disease (NAFLD). In the present study, the rats were injected with xylazine intraperitoneally for 28 consecutive days, and then serum and liver tissues were collected for analysis. Weight loss was observed in the 40 mg\/kg group and elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. Histopathologic examination showed hepatic steatosis, necrosis, and fibrosis. By mRNA sequencing, 192 upregulated genes and 277 downregulated genes were found in the 40 mg\/kg group, and the PPAR signaling pathway was ranked first in the KEGG pathway analysis. Four genes in the PPAR signaling pathway,\n                    <jats:italic>Fabp5<\/jats:italic>\n                    ,\n                    <jats:italic>Acox2<\/jats:italic>\n                    , and\n                    <jats:italic>Cpt2<\/jats:italic>\n                    , were also verified in the 40 mg\/kg group by RT\u2010qPCR analysis and western blot. Our results demonstrated that long\u2010term injection of xylazine causes NAFLD and the PPAR signaling pathway plays a core role in the process of xylazine\u2010associated liver injury.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70101","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T08:29:38Z","timestamp":1734510578000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Repeated Injection of Xylazine Causes Liver Injury Through the PPAR Signaling Pathway in Rats"],"prefix":"10.1002","volume":"39","author":[{"given":"Shanyong","family":"Yi","sequence":"first","affiliation":[{"name":"Xinxiang Key Laboratory of Forensic Toxicology, School of Forensic Medicine Xinxiang Medical University Xinxiang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Mai","sequence":"additional","affiliation":[{"name":"Faculty of Forensic Medicine, 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