title: Nicorandil attenuates neuronal mitochondrial dysfunction and oxidative stress associated with murine model of vascular calcification.
abstract: Evidences suggest that the presence of chronic kidney disease (CKD) is associated with cerebrovascular diseases related cognitive decline in dialysis patients. As mitochondrial dysfunction is implicated in neurodegenerative disorders, we hypothesized that changes in brain mitochondria occur due to vascular calcification induced by renal failure and the opening of the mitochondrial potassium channel using nicorandil may prevent its dysfunction. Brain tissues from rats with vascular calcification were studied. Nicorandil (7.5 mg/kg b.wt.) was given either concomitantly or after the induction of calcification. The brain tissues were evaluated for antioxidant capacity, mitochondrial enzymes and oxidative phosphorylation efficiency along with the progression of calcification. The results suggested that renal failure, elevated the calcium, phosphorus product in the brain. The brain cytoplasm and mitochondrial fractions showed an elevated TBARS and a corresponding decline in the antioxidant enzymes, indicating a sev ere oxidative stress. The elevated brain mitochondrial enzymes like NADH dehydrogenase, and succinate dehydrogenase in the disease control groups, reversed to the near control level after nicorandil treatment. We observed that nicorandil was more effective when given after calcification. It reduced the biochemical alterations associated with calcium and phosphorous toxicity in the brain, by preserving mitochondria, the key target for treating neurodegenerative diseases.
authors.affiliation: Vascular Biology Lab, SASTRA University, Thanjavur, India.
authors.forename: Sriram
authors.initials: S
authors.lastname: Ravindran
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Thanjavur, India.
authors.forename: Krithika
authors.initials: K
authors.lastname: Swaminathan
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Thanjavur, India.
authors.forename: Abhinaya
authors.initials: A
authors.lastname: Ramesh
authors.affiliation: Vascular Biology Lab, SASTRA University, Thanjavur, India, kurian@scbt.sastra.edu.
authors.forename: Gino A
authors.initials: GA
authors.lastname: Kurian
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004334:Drug Administration Schedule; D016166:Free Radical Scavengers / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000209:etiology; D020108:Nicorandil / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000175:diagnosis; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D061205:Vascular Calcification / Q000209:etiology / Q000517:prevention & control*; D014803:Vitamin B Complex / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016166:Free Radical Scavengers; D015395:Histocompatibility Antigens Class I; D017392:Thiobarbituric Acid Reactive Substances; D014803:Vitamin B Complex; D020108:Nicorandil; D010758:Phosphorus; D002374:Catalase; D002118:Calcium