title: Investigating the effect of antioxidant treatment on the protective effect of preconditioning in anesthetized rabbits.
abstract: Reactive oxygen and nitrogen species are critical in preconditioning (PC). We sought to determine the effect of N-2-mercaptopropionyl glycine (MPG) on infarct size and on the oxidative status. Rabbits were exposed to 30-minute regional ischemia of the heart, which was followed by 3-hour reperfusion: (1) a control group without further intervention, (2) a PC1 group that was subjected to one cycle of PC, (3) a PC4 group that was subjected to 4 cycles of PC, (4) an MPG group that was treated with MPG for 60 minutes, starting 10 minutes before reperfusion, (5) MPG-PC1, and (6) the MPG-PC4 groups that were treated with the same dose of MPG and with 1 or 4 cycles of PC, respectively. Blood samples were drawn and collected for metabonomic analysis. In another series of experiments, 6 groups respective to the described ones were subjected to 30-minute regional ischemia of the heart and 20 minutes of reperfusion, after which pieces of heart tissue were quickly excised for malondialdehyde, nitrotyrosine, and glutathione content assessment. All PC and MPG groups developed smaller infarct size compared with control (16.5% ± 3.9%, 13.7% ± 3.1%, 18.6% ± 5.0%, 9.7% ± 2.0%, 15.0% ± 2.8% vs. 48.05% ± 7.2%; P < 0.05). MPG did not prevent lipid peroxidation and nitrotyrosine formation but enhanced the glutathione content. PC and MPG induced similar nuclear magnetic resonance changes. Long MPG infusion reduces the infarct size without abolishing the effect of PC, providing novel insights into the activity of MPG in PC.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis, Athens, Greece. jandread@pharm.uoa.gr
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreadou
authors.forename: Efstathios K
authors.initials: EK
authors.lastname: Iliodromitis
authors.forename: Vassilios
authors.initials: V
authors.lastname: Souridis
authors.forename: Eftihios
authors.initials: E
authors.lastname: Prokovas
authors.forename: Sarantos
authors.initials: S
authors.lastname: Kostidis
authors.forename: Anastasia
authors.initials: A
authors.lastname: Zoga
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Dagres
authors.forename: Anna
authors.initials: A
authors.lastname: Tsantili-Kakoulidou
authors.forename: Dimitrios Th
authors.initials: DT
authors.lastname: Kremastinos
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mikros
authors.forename: Maria
authors.initials: M
authors.lastname: Anastasiou-Nana
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007262:Infusions, Intravenous; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D015227:Lipid Peroxidation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D013997:Time Factors; D008625:Tiopronin / Q000008:administration & dosage / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000975:Antioxidants; C002744:3-nitrotyrosine; D014443:Tyrosine; D008625:Tiopronin; D005978:Glutathione