Application of NMR-based metabonomics in the investigation of myocardial ischemia-reperfusion, ischemic preconditioning and antioxidant intervention in rabbits.
NMR based metabonomics was applied in rabbit plasma samples during myocardial ischemia-reperfusion injury, with the following interventions: (1) Control (no intervention); (2) ischemic preconditioning (IpC); (3) administration of melatonin; (4) IpC+administration of melatonin; (5) treatment of the indole derivative C6458. The (1)H NMR signal intensity ratio of lactate/glucose was found to increase in Control samples during reperfusion compared to baseline, while lactate+alanine/acetate was decreased suggesting impairment of aerobic glycolysis and concomitant lipid utilization. In contrast, after IpC or treatment with C6458, the lactate/glucose ratio was similar to baseline in accordance with the previously reported decrease in infarct size. Multivariate statistical methods such as Principal Component Analysis (PCA), and Discriminant Analysis (DA) were used for the discrimination of samples. The use of ANOVA variable preselection prior to PCA was advantageous in producing adequate models. PCA could classify the Control group in three clusters according to the condition of the heart (baseline-ischemia-reperfusion) while in the IpC groups no classification was evident. PCA discrimination upon treatment with melatonin and C6458 provided further evidence of their effect on the metabolic profile. The supervised DA resulted in fine discrimination between the different subgroups. Plasma NMR spectra in combination with pattern recognition techniques proved to be an efficient and simple method to depict the metabolic changes produced upon ischemia-reperfusion of the myocardium.
Constantinou
Maria A
MA
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimioupolis Zografou, 157 71 Athens, Greece.
Tsantili-Kakoulidou
Anna
A
Andreadou
Ioanna
I
Iliodromitis
Efstathios K
EK
Kremastinos
Dimitrios Th
DT
Mikros
Emmanuel
E
D000085:Acetates / Q000097:blood; D000409:Alanine / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D016002:Discriminant Analysis; D007211:Indoles / Q000097:blood / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D019344:Lactic Acid / Q000097:blood; D008055:Lipids / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008550:Melatonin / Q000097:blood / Q000494:pharmacology; D015999:Multivariate Analysis; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D025341:Principal Component Analysis; D011817:Rabbits; D014230:Triazoles / Q000097:blood / Q000494:pharmacology
C475199:3-((1H-1-indolyl)methyl) -4-amino 4,5-dihydro-1H,1,2,4 triazole-5-thione; D000085:Acetates; D000975:Antioxidants; D001786:Blood Glucose; D007211:Indoles; D008055:Lipids; D004364:Pharmaceutical Preparations; D014230:Triazoles; D019344:Lactic Acid; D008550:Melatonin; D000409:Alanine