Niacin Ameliorates Kidney Warm Ischemia and Reperfusion Injury-Induced Ventricular Dysfunction and Oxidative Stress and Disturbance in Mitochondrial Metabolism in Rats

•Kidney ischemia/reperfusion injury induces myocardial lipid peroxidation and promotes use of more free fatty acid for adenosine triphosphate production, and thus reduces cardiac function.•Niacin treatment protects the heart against kidney ischemia/reperfusion injury-induced myocardial dysfunction, potentially through reducing myocardial oxidative stress, and improves mitochondrial metabolism.

ObjectiveKidney ischemia and reperfusion (I/R) injury-associated acute and chronic kidney injury often leads to cardiac dysfunction, which may involve depletion of intracellular NAD+ (the oxidized form of the nicotinamide adenine dinucleotide coenzyme) and reduction in intracellular adenosine triphosphate (ATP) levels, resulting in mitochondrial dysfunction. We examined whether treatment with niacin, an antioxidant and a component of NAD+, protects cardiac function and improves myocardial mitochondrial metabolism during kidney I/R injury.MethodsStudies were performed in Sprague-Dawley male rats divided into sham-operated, kidney I/R, and niacin-treated kidney I/R groups. Niacin was administered 3 days before the ischemia through 7 days of reperfusion. Kidney ischemia was conducted by bilateral occlusion of renal pedicles for 45 minutes, followed by releasing the clamps and closing the abdominal incision. After 7 days of reperfusion, we measured the cardiac function using a simultaneous pressure-volume catheter, cardiac biomarker (troponin T; cTnT), and kidney injury marker (creatinine and blood urea nitrogen). Myocardial malondialdehyde level and peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α mRNA expression also were measured.ResultsKidney I/R injury impairs cardiac function, induces myocardial and kidney injury, and markedly increases myocardial PGC-1α mRNA expression, suggesting utilizing more free fatty acid for ATP production. Niacin treatment improved cardiac function, reduced oxidative stress, and sustained PGC-1α expression (P < .05).ConclusionsKidney I/R-associated cardiac dysfunction is likely associated with increases in myocardial lipid peroxidation and utilizing more free fatty acid for ATP production. Niacin improves mitochondrial metabolism and reduced myocardial oxidative stress.