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This study investigated the impact of trimetazidine (a metabolic modulator\u2010antianginal drug; TMZ), against FA\u2010induced AKI.\u00a0AKI was induced by FA (250\u2009mg\/kg, ip) in mice. Two doses of TMZ were administered orally for 10 days.\u00a0Administration of TMZ at a high dose (20\u2009mg\/kg) exhibited significant decreases in the renal somatic index (RSI), serum levels of lactate dehydrogenase (LDH), creatinine (Cr), blood urea nitrogen (1), and proteins level in urine. Moreover, TMZ significantly increased creatinine clearance (CCr), serum albumin, urine creatinine, and urine urea levels. This improvement in markers of kidney damage was associated with marked renal antioxidant effects (\u2193NO and \u2193lipid peroxidation, normalized reduced glutathione (GSH) level and superoxide dismutase (SOD) activity, and increased HIF\u20101\u03b1\/HO\u20101 level). Furthermore, TMZ significantly decreased FA\u2010induced expression of MPO and inflammatory cytokine IL\u201018, TNF\u2010\u03b1, and NF\u2010\u03baB p65 subunit. Renal apoptosis, along with apoptotic markers, were enhanced by FA injection and suppressed by TMZ administration (\u2193Caspase\u20103, \u2193Bax, and \u2191Bcl2 expression). Finally, TMZ amended FA\u2010induced histopathological changes in kidneys.\u00a0By mitigating functional alteration, oxidative stress, and preventing the development of inflammatory and apoptosis signals, TMZ provides dose\u2010dependent defense against FA\u2010induced AKI mainly via stimulation of hypoxia\u2010inducible factor\u20101 alpha (HIF\u20101\u03b1)\/heme oxygenase\u20101 (HO\u20101) pathway.<\/jats:p>","DOI":"10.1002\/jbt.23011","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T12:02:55Z","timestamp":1645531375000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Beneficial effect of trimetazidine on folic acid\u2010induced acute kidney injury in mice: Role of HIF\u20101\u03b1\/HO\u20101"],"prefix":"10.1002","volume":"36","author":[{"given":"Rehab S.","family":"Abdelrahman","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, Taibah University Al\u2010Madinah Al\u2010Munawarah Saudi Arabia"},{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy, Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramy A.","family":"Abdelsalam","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of medicine, Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7082-481X","authenticated-orcid":false,"given":"Marwa S.","family":"Zaghloul","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy, Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030649"},{"issue":"2","key":"e_1_2_11_3_1","first-page":"85","volume":"37","author":"Makris K.","year":"2016","journal-title":"Clin. 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