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Renal fibrosis is considered to be one of the most important conditions, as it may be the result of excessive extracellular matrix protein production and deposition, or prolonged exposure to nephrotoxic substances or drugs. Unfortunately, no suitable therapies or medications are currently available to prevent renal fibrosis. We conducted this study for the evaluation of the protective potential of vanillin by reversing TAA (250\u2009mg\/kg TAA for 6\u2009weeks) induced renal injury in rats. The concentrations of the proteins tumour necrosis factor alpha (TNF\u03b1), interleukin\u20106 (IL\u20106), extracellular signal regulated kinase 1\/2 (Erk1\/2), and transforming growth factor beta\u20101 (TGF\u2010\u03b21) in kidney tissues were assessed using ELISA. Kidney Injury Molecule\u20101 (KIM\u20101) and mothers against decapentaplegic homologue 2, 3 (SMAD 2, 3) expressions were evaluated using real time PCR. We also estimated the expression of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) using immunohistochemistry. Treatment with vanillin (100\u2009mg\/kg) significantly ameliorated kidney Injury and improved the kidney function. Vanillin treatment also significantly decreased the malondialdehyde (MDA) content, and elevated glutathione peroxidase <jats:bold>(<\/jats:bold>GPx) and catalase (CAT) activities in kidney tissues. Vanillin also reduced \u03b1\u2010SMA renal expression and TNF\u03b1, IL\u20106, TGF\u2010\u03b21, and Erk1\/2 renal levels. Vanillin significantly decreased the expression of the genes encoding KIM\u20101 and SMAD 2, 3 and ameliorated histological abnormalities in kidney architecture. Our molecular docking findings showed that vanillin has a good binding mode inside TGF\u2010\u03b2 type I receptors (ALK5) biding site.<\/jats:p>","DOI":"10.1002\/cbf.3686","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T04:25:50Z","timestamp":1643430350000},"page":"189-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Vanillin attenuates thioacetamide\u2010induced renal assault by direct and indirect mediation of the <scp>TGF\u03b2<\/scp>, <scp>ERK<\/scp> and Smad signalling pathways in rats"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9593-4687","authenticated-orcid":false,"given":"Heba A.","family":"Metwaly","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Faculty of Pharmacy Alexandria University  Alexandria Egypt"},{"name":"Department of Biochemistry, Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman M.","family":"El\u2010Eraky","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman E.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled K.","family":"Kandil","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"El\u2010Sayed","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayra M.","family":"El\u2010Tabakh","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr M.","family":"Motawea","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmi A.","family":"Ali","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maher Z.","family":"Jabban","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona E.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walaa H.","family":"Abdelfattah","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Delta University  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A.","family":"Elmorsy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Mansoura University  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal M. 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