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Despite the recently depicted antifibrotic effects of alpha-lipoic acid (ALA), however, its modulatory effects on HSCs autophagy remain unverified. Our study aimed to elucidate the underlying antifibrotic mechanisms through which ALA mediates HSC autophagy and apoptosis. Liver fibrosis was induced via thioacetamide (TAA) intoxication in rats; TAA-intoxicated rats were treated with either silymarin or ALA. Effect of ALA on biochemical parameters and immunohistopathological examinations was measured and compared to silymarin. ALA restored normal hepatic architecture (S1 vs. S4), liver functions, hepatic glutathione, and transforming growth factor-\u03b21 levels. ALA ameliorated hepatic levels of malondialdehyde, platelet-derived growth factor, tissue inhibitor metalloproteinases-1, hydroxyproline, and expression of alpha-smooth muscle actin. Moreover, ALA significantly reduced messenger RNA expression of LC3-II genes and triggered caspase-3 expression. Interestingly, ALA exhibited superior activities over silymarin regarding suppression of proliferation, activation and autophagy of HSCs, collagen deposition, and induction of HSCs apoptosis. In conclusion, treatment of TAA-intoxicated rats with ALA inhibited autophagy and induced apoptotic clearance of activated HSCs. Accordingly, this study provides mechanistic insights into the possible applicability of ALA in the treatment of hepatic fibrosis.<\/jats:p>","DOI":"10.1177\/0960327119891212","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T05:49:12Z","timestamp":1575438552000},"page":"440-450","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["\u03b1-Lipoic acid modulates liver fibrosis: A cross talk between TGF-\u03b21, autophagy, and apoptosis"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4632-3510","authenticated-orcid":false,"given":"WH","family":"El-Maadawy","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"OA","family":"Hammam","sequence":"additional","affiliation":[{"name":"Department of Pathology, Theodor 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