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Pirfenidone is a novel broad\u2010spectrum anti\u2010fibrosis agent used for treating various kinds of tissue fibrosis. The present study will evaluate the effects of Pirfenidone on liver injury in high\u2010fat diet (HFD)\u2010fed mice to evaluate the value of Pirfenidone in treating NAFLD.\u00a0The pathology of NAFLD was simulated by feeding mice with an HFD in the present study, followed by treating the HFD mice with 150\u00a0and 300\u2009mg\/kg\/day Pirfenidone once a day.\u00a0The pathological state of HFD mice was identified by the elevated liver weight, promoted serum triglyceride (TG), total cholesterol (TC), and low\u2010density lipoprotein cholesterol (LDL\u2010C) levels, declined serum high\u2010density lipoprotein cholesterol (HDL\u2010C) levels, increased alanine\u00a0aminotransferase and aspartate aminotransferase activity, and histopathological changes to the liver tissues, all of which were dramatically ameliorated by 150\u00a0and 300\u2009mg\/kg Pirfenidone administration. Furthermore, the excessive production of interleukin\u20101\u03b2 (IL\u20101\u03b2), tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), and IL\u20106, as well as upregulated phosphorylated nuclear factor kappa\u2010B (p\u2010 NF\u2010\u03baB p65), were observed in HFD\u2010fed mice, but significantly reversed by Pirfenidone. Finally, activated oxidative stress, identified by promoted malondialdehyde (MDA) levels and declined catalase (CAT) activity, was observed in HFD\u2010fed mice, accompanied by the downregulation of nuclear factor erythroid 2\u2010related factor 2 (Nrf2) and sterol\u2010regulatory element\u2010binding proteins\u20101c (SREBP\u20101c). After the treatment with Pirfenidone, oxidative stress was greatly mitigated.\u00a0Our results imply that Pirfenidone ameliorated the progression of NAFLD by mediating inflammation and oxidative stress.<\/jats:p>","DOI":"10.1002\/jbt.23251","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T10:29:55Z","timestamp":1667384995000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Pirfenidone attenuates nonalcoholic fatty liver disease through activation of the nuclear factor erythroid 2\u2010related factor 2 (Nrf2) signaling pathway"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8020-7973","authenticated-orcid":false,"given":"Rong","family":"Xie","sequence":"first","affiliation":[{"name":"Department of the Traditional Chinese Medicine The First Affiliated Hospital of Hainan Medical College  Hainan Province Haikou City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaodong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, School of Medicine Xiamen University  Fujian Province Xiamen City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of the Traditional Chinese Medicine The First Affiliated Hospital of Hainan Medical College  Hainan Province Haikou City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Hainan Medical University  Hainan Province Haikou City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bangliang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Hainan Medical University  Hainan Province Haikou City China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.2298"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50161"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i27.2974"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1301\/002966402320387224"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520701514529"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8416763"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i39.14205"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000282083"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21984"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i3.711"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0057-2017"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0350-9"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-021-10175-w"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40523"},{"key":"e_1_2_11_17_1","first-page":"e931143","volume":"27","author":"Jiang J.","year":"2021","journal-title":"Med. 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