Different responses of fluvastatin to cholesterol-induced oxidative modifications in rabbits: evidence for preventive effect against DNA damage

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dc.contributor.authorSevin, Gulnur
dc.contributor.authorYasa, Mukadder
dc.contributor.authorAkcay, Delen Yasemin
dc.contributor.authorKirkali, Guldal
dc.contributor.authorKerry, Zeliha
dc.date.accessioned2019-10-27T21:52:05Z
dc.date.available2019-10-27T21:52:05Z
dc.date.issued2013
dc.departmentEge Üniversitesien_US
dc.description.abstractHypercholesterolemia is a major risk factor for atherosclerosis and related occlusive vascular diseases. We investigated the effect of low-dose fluvastatin (2 mg kg-1 day-1) on antioxidant enzyme activities [superoxide dismutase (SOD), catalase], vascular reactivity changes and oxidatively induced DNA damage in early stage of atherosclerosis in hypercholesterolemic rabbits. The animals were divided into three groups each composed of 10 rabbits. The control group received a regular rabbit chow diet, and the cholesterol group had hypercholesterolemic diet (2%, 4 weeks). The fluvastatin group was given hypercholesterolemic diet plus fluvastatin. Dietary intake of cholesterol significantly increased total cholesterol levels in rabbits (control, 0.85 +/- 0.29; cholesterol, 12.04 +/- 4.61; fluvastatin, 8.07 +/- 2.72 mmol l-1 ). Hypercholesterolemic diet revealed discernible fatty streaks in arcus aortae. Fluvastatin significantly reduced the areas of the lesions. The diet significantly increased SOD activities in both erythrocyte and tissue. Treatment with fluvastatin normalized the increased activity of SOD in both erythrocyte and aortic tissues from the cholesterol group. Cholesterol feeding decreased the sensitivity to acetylcholine, and treatment with fluvastatin significantly restored the diminished sensitivity to acetylcholine in thoracic aortae. Cholesterol feeding caused oxidatively induced DNA damage in liver tissues determined by the increased levels of 8-hydroxyguanine (8-OH-Gua) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua). Fluvastatin decreased only FapyGua level in liver. In conclusion, our results may suggest that fluvastatin seems to play a protective role on high cholesterol-induced oxidative stress and DNA damage. Copyright (c) 2012 John Wiley & Sons, Ltd.en_US
dc.description.sponsorshipEge University Scientific Research FoundationEge University [99 ECZ 016]en_US
dc.description.sponsorshipThe authors are grateful to Prof. E. Sozmen (Faculty of Medicine, Department of Biochemistry, Ege University Izmir, Turkey) for helping with biochemical measurements, Prof. E. Ozer (Faculty of Medicine, Department of Pathology, Dokuz Eylul University, Inciralti, Izmir, Turkey) for the morphological examinations and Prof M. Dizdaroglu (Biochemical Science Division, National Institute of Standards and Technology, Gaithersburg, MD, USA) for DNA measurements. This work was supported by The Ege University Scientific Research Foundation (grant no. 99 ECZ 016 to GS).en_US
dc.identifier.doi10.1002/cbf.2903en_US
dc.identifier.endpage332en_US
dc.identifier.issn0263-6484
dc.identifier.issue4en_US
dc.identifier.pmid23055364en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage325en_US
dc.identifier.urihttps://doi.org/10.1002/cbf.2903
dc.identifier.urihttps://hdl.handle.net/11454/47486
dc.identifier.volume31en_US
dc.identifier.wosWOS:000319991200009en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWiley-Blackwellen_US
dc.relation.ispartofCell Biochemistry and Functionen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectatherosclerosisen_US
dc.subjectfluvastatinen_US
dc.subjecthypercholesterolemiaen_US
dc.subjectrabbiten_US
dc.subjectoxidatively induced DNA damageen_US
dc.subject8-hydroxyguanineen_US
dc.subject2en_US
dc.subject6-diamino-4-hydroxy-5-formamidopyrimidineen_US
dc.titleDifferent responses of fluvastatin to cholesterol-induced oxidative modifications in rabbits: evidence for preventive effect against DNA damageen_US
dc.typeArticleen_US

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