S T Tai1, Y H Fu2, Y C Yang2, J J Wang3. 1. Division of Cardiology, Saint Paul's Hospital, Taoyuan, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. 2. School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. 3. School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: 078625@mail.fju.edu.tw.
Abstract
OBJECTIVE: Kidney 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. METHODS: Studies 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. RESULTS: Kidney 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). CONCLUSIONS: Kidney 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.
OBJECTIVE:Kidney 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. METHODS: Studies 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 ureanitrogen). Myocardial malondialdehyde level and peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α mRNA expression also were measured. RESULTS:Kidney 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). CONCLUSIONS: Kidney 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.