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This study aimed to investigate the potential hepatoprotective effects of L-carnitine (LCR), a mitochondrial cofactor with antioxidant and anti-apoptotic properties, in a rat model of MTX-induced hepatotoxicity. Twenty-four male Wistar rats were randomly divided into four groups: Control, MTX (20\u00a0mg\/kg, i.p., single dose), LCR (100\u00a0mg\/kg\/day, oral) and MTX\u2009+\u2009LCR. After 10\u00a0days, liver tissues were examined histopathologically, immunohistochemically for CD38 and GLUT1, and by qPCR for BAX and BCL2 expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also measured. MTX administration induced histological injury, upregulated CD38 and GLUT1 expression and altered apoptosis-related genes (BAX\u2191, BCL2\u2193) with a trend toward elevated ALT and AST levels. LCR co-treatment improved hepatic histoarchitecture, reduced CD38 and GLUT1 expression and partially normalized BAX\/BCL2 expression, with a tendency to restore serum enzyme activity. L-carnitine may attenuate MTX-induced hepatotoxicity by modulating oxidative stress, metabolic stress and apoptotic signaling. These findings suggest a potential role for L-carnitine as an adjuvant to improve hepatic safety during MTX therapy.<\/jats:p>","DOI":"10.1007\/s00210-026-05196-x","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:41:55Z","timestamp":1774334515000},"page":"13319-13330","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["L-carnitine protects against methotrexate-induced hepatotoxicity via regulation of apoptosis and metabolic pathways"],"prefix":"10.1007","volume":"399","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7442-7232","authenticated-orcid":false,"given":"Sakir","family":"Pekgoz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2766-2349","authenticated-orcid":false,"given":"Zafer","family":"Usta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4117-0455","authenticated-orcid":false,"given":"Yagmur","family":"Kara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1835-1082","authenticated-orcid":false,"given":"Ozlem","family":"Ozmen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"issue":"8","key":"5196_CR1","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1007\/s00210-020-01843-z","volume":"393","author":"RM Abdelaziz","year":"2020","unstructured":"Abdelaziz RM, Abdelazem AZ, Hashem KS, Attia YA (2020) Protective effects of hesperidin against MTX-induced hepatotoxicity in male albino rats. 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All procedures were conducted in accordance with Directive 2010\/63\/EU on the protection of animals used for scientific purposes.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All experimental procedures were approved by the Burdur Mehmet Akif Ersoy University Animal Experiments Local Ethics Committee (Approval No: 1379, dated 02.10.2024). A total of 24 healthy male Wistar albino rats (250\u2013300\u00a0g) were used, with six animals per group (n\u2009=\u20096). All procedures were conducted in accordance with Directive 2010\/63\/EU on the protection of animals used for scientific purposes. This study was conducted within the scope of the S\u00fcleyman Demirel University Scientific Research Projects Coordination Unit (BAP) project (No: 9524).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Animal welfare statement"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}]}}