Trimetazidine protects low-density lipoproteins from oxidation and cultured cells exposed to H2O2 from DNA damage

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dc.contributor.authorTselepis, A.en
dc.contributor.authorDoulias, P. T.en
dc.contributor.authorLourida, E.en
dc.contributor.authorGlantzounis, G.en
dc.contributor.authorTsimoyiannis, E.en
dc.contributor.authorGalaris, D.en
dc.date.accessioned2015-11-24T16:51:48Z
dc.date.available2015-11-24T16:51:48Z
dc.identifier.issn0891-5849-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/9789
dc.rightsDefault Licence-
dc.subjectldlen
dc.subjectoxidized-ldlen
dc.subjectpaf-acetylhydrolaseen
dc.subjecthydrogen peroxideen
dc.subjectsingle cell gel electrophoresis (comet assay)en
dc.subjectglucose oxidaseen
dc.subjectjurkat cellsen
dc.subjectfree radicalsen
dc.subjectplatelet-activating-factoren
dc.subjectdegrading acetylhydrolaseen
dc.subjectmitochondrial-functionen
dc.subjectreperfusion injuryen
dc.subjecthuman plasmaen
dc.subjectcomet assayen
dc.subjectin-vitroen
dc.subjectldlen
dc.subjectischemiaen
dc.subjectratsen
dc.titleTrimetazidine protects low-density lipoproteins from oxidation and cultured cells exposed to H2O2 from DNA damageen
heal.abstractTrimetazidine is a well-established anti-ischemic drug, which has been used for long time in the treatment of pathological conditions related with the generation of reactive oxygen species. However, although extensively studied, its molecular mode of action remains largely unknown. In the present study, the ability of trimetazidine to protect low-density lipoproteins (LDL) from oxidation and cultured cells from H2O2-induced DNA damage was investigated. Trimetazidine, tested at concentrations 0.02 to 2.20 mM, was shown to offer significant protection to LDL exposed to three different oxidizing systems, namely copper, Fe/ascorbate, and met-myoglobin/H2O2. The oxidizability of LDL was estimated by measuring, (i) the lag period, (ii) the maximal rate of conjugated diene formation, (iii) the total amount of conjugated dienes formed, (iv) the electrophoretic migration of LDL protein in agarose gels (REM), and (v) the inactivation of the enzyme PAF-acetylhydrolase present in LDL. In addition, the presence of trimetazidine decreased considerably the DNA damage in H2O2-exposed Jurkat cells in culture. H2O2 was continuously generated by the action of glucose oxidase at a rate of 11.8 +/- 1.5 muM per min (60 ng enzyme per 100 mu1), and DNA damage was assessed by the single cell gel electrophoresis assay (also called comet assay). The protection offered by trimetazidine in this system (about 30% at best) was transient, indicating modification of this agent during its action. These results indicate that trimetazidine can modulate the action of oxidizing agents in different systems. Although its mode of action is not clarified, the possibility that it acts as a lipid barrier permeable transition metal chelator is considered. (C) 2001 Elsevier Science Inc.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondary<Go to ISI>://000169257400003-
heal.identifier.secondaryhttp://ac.els-cdn.com/S0891584901005378/1-s2.0-S0891584901005378-main.pdf?_tid=c5dddbd0b41f5318be8dae718ed3023b&acdnat=1333111883_eb1e1dc000b0bd159980485524202470-
heal.journalNameFree Radical Biology and Medicineen
heal.journalTypepeer reviewed-
heal.languageen-
heal.publicationDate2001-
heal.publisherElsevieren
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείαςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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