Arbutin abrogates cisplatin-induced hepatotoxicity via upregulating Nrf2/HO-1 and suppressing genotoxicity, NF-?B/iNOS/TNF-? and caspase-3/Bax/Bcl2 signaling pathways in rats

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dc.contributor.authorOkkay, Irmak Ferah
dc.contributor.authorFamurewa, Ademola
dc.contributor.authorBayram, Cemil
dc.contributor.authorOkkay, Ufuk
dc.contributor.authorMendil, Ali Sefa
dc.contributor.authorSezen, Selma
dc.contributor.authorAyaz, Teslime
dc.date.accessioned2024-10-26T18:11:09Z
dc.date.available2024-10-26T18:11:09Z
dc.date.issued2024
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractBackground: Cisplatin is a potent anticancer agent widely employed in chemotherapy. However, cisplatin leads to toxicity on non-targeted healthy organs, including the liver. We investigated the hepatoprotective mechanism of arbutin (ARB), a glycosylated hydroquinone, against cisplatin-induced hepatotoxicity. Methods: Rats were orally administered with ARB (ARB1 = 50 mg/kg; ARB2 = 100 mg/kg) for 14 consecutive days against hepatotoxicity induced by a single dose of cisplatin (10 mg/kg) on day 15. Three days after the intraperitoneal cisplatin injection, serum and liver tissue were collected for subsequent analyses. Results: Cisplatin triggered marked increases in serum AST, ALT, and ALP activities, hepatic malondialdehyde (MDA) and reactive oxygen species (ROS) coupled with a considerable diminution in hepatic activities of superoxide dismutase (SOD), catalase (CAT) and the concentration of reduced glutathione (GSH). The gene expressions of interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF-alpha), and IL-6 were notably increased. The pre-administration of ARB1 and ARB2 reduced AST, ALT and ALP in serum and restored SOD, CAT, GSH, ROS, MDA and cytokine levels which was also evidenced by alleviated hepatic lesions. Further, cisplatin-induced prominent alterations in the gene expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), iNOS, NF-kappa B, Bax, Bcl-2, caspase-3 and 8-OHdG in the liver. Interestingly, ARB protected the liver and mitigated the cisplatin-induced alterations in serum AST, ALT, ALP, and reduced hepatic redox markers, 8-OdG, inflammatory markers and gene expressions. Conclusion: The findings demonstrate that ARB is a potential protective adjuvant against cisplatin-induced hepatotoxicity via inhibition of hepatic oxidative stress, inflammation, and apoptosis.
dc.identifier.doi10.1093/toxres/tfae075
dc.identifier.issn2045-452X
dc.identifier.issn2045-4538
dc.identifier.issue3
dc.identifier.pmid38770183
dc.identifier.scopus2-s2.0-85193832052
dc.identifier.scopusqualityQ3
dc.identifier.urihttps://doi.org/10.1093/toxres/tfae075
dc.identifier.urihttps://hdl.handle.net/20.500.12418/30542
dc.identifier.volume13
dc.identifier.wosWOS:001225533000001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherOxford Univ Press
dc.relation.ispartofToxicology Research
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectarbutin
dc.subjectapoptosis
dc.subjectcisplatin
dc.subjecthepatotoxicity
dc.subjectinflammation
dc.subjectoxidative stress
dc.titleArbutin abrogates cisplatin-induced hepatotoxicity via upregulating Nrf2/HO-1 and suppressing genotoxicity, NF-?B/iNOS/TNF-? and caspase-3/Bax/Bcl2 signaling pathways in rats
dc.typeArticle

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