Cannabidiol mitigates methotrexate-induced hepatic injury via SIRT-1/p53 signaling and mitochondrial pathways: reduces oxidative stress and inflammation

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dc.authorid0000-0003-3739-9580
dc.authorid0000-0002-1545-035X
dc.authorid0000-0003-3875-9365
dc.authorid0000-0002-3850-0137
dc.contributor.authorIlhan, Ilter
dc.contributor.authorAsci, Halil
dc.contributor.authorCandan, Ibrahim Aydin
dc.contributor.authorSavran, Mehtap
dc.contributor.authorImeci, Orhan Berk
dc.contributor.authorSevuk, Mehmet Abdulkadir
dc.date.accessioned2026-01-24T12:31:25Z
dc.date.available2026-01-24T12:31:25Z
dc.date.issued2025
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractMethotrexate (MTX), a widely used chemotherapeutic agent, often induces hepatotoxicity, limiting its clinical utility. Cannabidiol (CBD), derived from hemp, possesses antioxidant, anti-inflammatory, and antiapoptotic properties. This study aims to investigate CBD's protective effects against MTX-induced liver injury and elucidate the underlying mechanisms. Thirty-two female Wistar Albino rats were divided into four groups: control, MTX (20 mg/kg intraperitoneally [i.p.] once), MTX+CBD (20 mg/kg i.p. once + 5 mg/kg i.p. for seven days), and CBD (5 mg/kg, i.p. for seven days). Biochemical analyses of serum and liver tissues were performed to assess oxidative stress markers (total oxidant status, total antioxidant status, oxidative stress index), liver function tests (AST, ALT), and antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase). Histopathological and immunohistochemical examinations were conducted to evaluate liver tissue damage and TNF-alpha expression. Genetic analyses were performed to measure the expression levels of SIRT-1, p53, Bcl-2, and Bax genes using RT-qPCR. MTX administration increased oxidative stress markers, liver enzymes, TNF-alpha, p53, and Bax levels while decreasing antioxidant defenses and SIRT-1 expression. CBD administration reversed these alterations effectively. CBD mitigated MTX-induced hepatotoxicity by reducing oxidative stress, inflammation, and apoptosis. It activates antioxidant defenses via SIRT-1 upregulation, suppresses inflammation by reducing TNF-alpha, and prevents apoptosis by modulating p53, Bcl-2, and Bax gene expressions. These findings suggest CBD could be a promising therapeutic agent for chemotherapy-induced liver damage. Further research is warranted to explore additional pathways and broader molecular mechanisms.
dc.description.sponsorshipScientific Research Projects Coordination Unit of Suleyman Demirel University [TSG-2022-8783]
dc.description.sponsorshipThis study was supported by the Scientific Research Projects Coordination Unit of Suleyman Demirel University with project no. TSG-2022-8783.
dc.identifier.doi10.1080/01480545.2024.2425994
dc.identifier.endpage218
dc.identifier.issn0148-0545
dc.identifier.issn1525-6014
dc.identifier.issue1
dc.identifier.pmid39603835
dc.identifier.scopus2-s2.0-85210485850
dc.identifier.scopusqualityQ1
dc.identifier.startpage210
dc.identifier.urihttps://doi.org/10.1080/01480545.2024.2425994
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5863
dc.identifier.volume48
dc.identifier.wosWOS:001364543300001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherTaylor & Francis Ltd
dc.relation.ispartofDrug and Chemical Toxicology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20260121
dc.subjectMethotrexate
dc.subjectcannabidiol
dc.subjectSIRT-1
dc.subjectp53
dc.subjectoxidative stress
dc.titleCannabidiol mitigates methotrexate-induced hepatic injury via SIRT-1/p53 signaling and mitochondrial pathways: reduces oxidative stress and inflammation
dc.typeArticle

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