dc.contributor.author | Kılıç, Ülkan | |
dc.contributor.author | Kılıç, Ertuğrul | |
dc.contributor.author | Tuzcu, Zeynep | |
dc.contributor.author | Tuzcu, Mehmet | |
dc.contributor.author | Özercan, İbrahim | |
dc.contributor.author | Yılmaz, Ökkeş | |
dc.contributor.author | Şahin, Fikrettin | |
dc.contributor.author | Şahin, Kazım | |
dc.date.accessioned | 10.07.201910:49:13 | |
dc.date.accessioned | 2019-07-10T20:02:10Z | |
dc.date.available | 10.07.201910:49:13 | |
dc.date.available | 2019-07-10T20:02:10Z | |
dc.date.issued | 2013 | en_US |
dc.identifier.citation | Kılıç, Ü., Kılıç, E., Tuzcu, Z., Tuzcu, M., Özercan, İ., Yılmaz, Ö. ... Şahin, K. (2013). Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2/HO-1 pathway. Nutrition & Metabolism, 10(1). https://dx.doi.org/10.1186/1743-7075-10-7 | en_US |
dc.identifier.issn | 1743-7075 | |
dc.identifier.uri | https://dx.doi.org/10.1186/1743-7075-10-7 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12511/3572 | |
dc.description | WOS: 000314541600001 | en_US |
dc.description | PubMed ID: 23311701 | en_US |
dc.description.abstract | Background: Cisplatin, one of the most effective and potent anticancer drugs, is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side-effects such as nephrotoxicity and ototoxicity. Cisplatin chemotherapy induces a reduction in the antioxidant status, leading to a failure of the antioxidant defense against free-radical damage generated by antitumor drugs. Cisplatin-induced oxidative stress in the kidney was partially prevented by antioxidant treatments using superoxide dismutase, glutathione, selenium and flavonoids. Melatonin and its metabolites possess free-radical scavenging activity and it has been shown that they protect against cisplatin toxicity. However, the mechanism of the protective effects of melatonin against cisplatin-induced nephrotoxicity is still essentially unknown. We therefore designed this study to investigate the underlying mechanism of the protective effect of melatonin against cisplatin-induced renal damage in a rat nephrotoxicity model in vivo. Methods: Twenty eight 8-week-old male Wistar rats were divided into four groups of control, melatonin treatment (4 mg/kg b.w i.p. for 10 days), cisplatin treatment (7 mg/kg b.w., i.p.) and melatonin and cisplatin combination treatment. Serum urea nitrogen (urea-N) and creatinine levels were measured. Histopathological changes were evaluated. In addition, we analyzed the expression levels of HO-1, Nrf2, NF-kappa B and AP-1 in Western blot analysis. Results: Both serum creatinine and urea nitrogen increased significantly following cisplatin administration alone; these values decreased significantly with melatonin co-treatment of cisplatin-treated rats. Histological analysis showed that cisplatin caused damage in the proximal tubular cells in the kidneys of cisplatin-treated rats; these changes were reversed by melatonin co-treatment. Upon Western blot analysis, melatonin treatment increased Nrf2 accumulation in the nuclear fraction, and increased the expression of HO-1 in the cytosolic fraction as compared to the cisplatin-treated rats. Expressions of NF-kappa B p65 and AP-1 were increased significantly in the kidneys of rats treated with cisplatin compared with the expression in the kidneys from the control, melatonin-only-treated and melatonin co-treated rats. Conclusion: Our present data suggest that melatonin attenuates cisplatin-induced nephrotoxicity possibly by modulating Nrf2/HO-1 signaling. | en_US |
dc.description.sponsorship | EMBO (European Molecular Biology Organization) installation grant; Turkish Academy of Sciences (TUBA) | en_US |
dc.description.sponsorship | This work was supported by EMBO (European Molecular Biology Organization) installation grant and The Turkish Academy of Sciences (TUBA). | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Biomed Central Ltd | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Nephrotoxicity | en_US |
dc.subject | Nrf2/HO-1 signaling | en_US |
dc.subject | Melatonin | en_US |
dc.subject | Oxidative stress | en_US |
dc.title | Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2/HO-1 pathway | en_US |
dc.type | article | en_US |
dc.relation.ispartof | Nutrition & Metabolism | en_US |
dc.department | İstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı | en_US |
dc.authorid | 0000-0001-6494-8923 | en_US |
dc.identifier.volume | 10 | en_US |
dc.identifier.issue | 1 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.identifier.doi | 10.1186/1743-7075-10-7 | en_US |
dc.identifier.wosquality | Q2 | en_US |
dc.identifier.scopusquality | Q1 | en_US |