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Balb-C mice were randomly allocated into five groups (10 each): (i) control; (ii) mice were injected intraperitoneally with 50 \u03bcL carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) in corn oil in a dose of 0.6 \u03bcL\/g three times per week for four weeks; (iii) linagliptin was administered orally in a daily dose of 10 mg\/kg simultaneously with CCl<jats:sub>4<\/jats:sub>; (iv) silymarin was administered orally in a daily dose of 200 mg\/kg concomitantly with CCl<jats:sub>4<\/jats:sub>; and (v) only linagliptin was administered. Hepatic injury was manifested in the CCl<jats:sub>4<\/jats:sub> group by elevation of biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)), and hepatic fibrosis was evident histopathologically by increased METAVIR score and immunostaining expression of alpha-smooth muscle actin (\u03b1-SMA), as well as increased liver tissue oxidative stress parameters, transforming growth factor-\u03b21 (TGF-\u03b21), and mammalian target of rapamycin (mTOR). Linagliptin was able to stop the progression of liver fibrosis, evident histopathologically with reduced METAVIR score and \u03b1-SMA expression. The possible mechanism may be via suppression of oxidative stress, TGF-\u03b21, and mTOR, which was associated with improvement of serum biochemical parameters ALT and AST. In conclusion, linagliptin might help to protect the liver against persistent injury-related consequences. <\/jats:p>","DOI":"10.1139\/cjpp-2020-0049","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T21:35:49Z","timestamp":1596058549000},"page":"294-302","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Hepatoprotective effect of linagliptin against liver fibrosis induced by carbon tetrachloride in mice"],"prefix":"10.1139","volume":"99","author":[{"given":"Maaly","family":"Abd Elmaaboud","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidy","family":"Khattab","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahinaz","family":"Shalaby","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.2337\/db18-1841-P"},{"key":"refg3\/ref3","first-page":"882","volume":"61","author":"Beutler E.","year":"1963","journal-title":"J. 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