Trimetazidine protects low-density lipoproteins from oxidation and cultured cells exposed to H2O2 from DNA damage
Φόρτωση...
Ημερομηνία
Συγγραφείς
Tselepis, A.
Doulias, P. T.
Lourida, E.
Glantzounis, G.
Tsimoyiannis, E.
Galaris, D.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Elsevier
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Free Radical Biology and Medicine
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
Trimetazidine 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.
Περιγραφή
Λέξεις-κλειδιά
ldl, oxidized-ldl, paf-acetylhydrolase, hydrogen peroxide, single cell gel electrophoresis (comet assay), glucose oxidase, jurkat cells, free radicals, platelet-activating-factor, degrading acetylhydrolase, mitochondrial-function, reperfusion injury, human plasma, comet assay, in-vitro, ldl, ischemia, rats
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
<Go to ISI>://000169257400003
http://ac.els-cdn.com/S0891584901005378/1-s2.0-S0891584901005378-main.pdf?_tid=c5dddbd0b41f5318be8dae718ed3023b&acdnat=1333111883_eb1e1dc000b0bd159980485524202470
http://ac.els-cdn.com/S0891584901005378/1-s2.0-S0891584901005378-main.pdf?_tid=c5dddbd0b41f5318be8dae718ed3023b&acdnat=1333111883_eb1e1dc000b0bd159980485524202470
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας