Our previous study shows that
nicotinamide adenine dinucleotide phosphate (
NADPH) plays an important role in protecting against
cerebral ischemia injury. In this study we investigated whether
NADPH exerted cardioprotection against
myocardial ischemia/reperfusion (I/R) injury. To induce myocardial I/R injury, rats were subjected to
ligation of the left anterior descending branch of coronary artery for 30 min followed by reperfusion for 2 h. At the onset of reperfusion,
NADPH (4, 8, 16 mg· kg-1· d-1, iv) was administered to the rats. We found that
NADPH concentrations in plasma and heart were significantly increased at 4 h after
intravenous administration. Exogenous
NADPH (8-16 mg/kg) significantly decreased
myocardial infarct size and reduced serum levels of
lactate dehydrogenase (LDH) and cardiac
troponin I (
cTn-I). Exogenous
NADPH significantly decreased the apoptotic rate of cardiomyocytes, and reduced the cleavage of PARP and
caspase-3. In addition, exogenous
NADPH reduced mitochondrial vacuolation and increased mitochondrial membrane
protein COXIV and TOM20, decreased BNIP3L and increased Bcl-2 to protect mitochondrial function. We conducted in vitro experiments in neonatal rat cardiomyocytes (NRCM) subjected to
oxygen-
glucose deprivation/restoration (OGD/R). Pretreatment with
NADPH (60, 500 nM) significantly rescued the cell viability and inhibited OGD/R-induced apoptosis. Pretreatment with
NADPH significantly increased the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in OGD/R-treated NRCM. Compound C, an AMPK inhibitor, abolished
NADPH-induced AMPK phosphorylation and cardioprotection in OGD/R-treated NRCM. In conclusion, exogenous
NADPH exerts cardioprotection against myocardial I/R injury through the activation of AMPK/mTOR pathway and inhibiting mitochondrial damage and cardiomyocyte apoptosis.
NADPH may be a potential candidate for the prevention and treatment of myocardial ischemic diseases.