Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nitrovasodilator, nicorandil, is a clinically effective antianginal agent. We tested whether nicorandil may also possess anti-free-radical characteristics, since the nicotinamide moiety of its molecular structure is a known hydroxyl radical scavenger. In vitro production of hydroxyl radicals by hypoxanthine plus xanthine oxidase in the presence of iron produced a marked degradation of deoxyribose. Nicorandil and the structural analogs, nicotinic acid and nicotinamide, produced significant inhibition of deoxyribose breakdown at concentrations equipotent to the classical hydroxyl radical scavenger, mannitol. Nicorandil also produced a concentration-dependent inhibition of superoxide anion production by canine neutrophils that were activated with either phorbol myristate acetate (PMA) or opsonized zymosan. This inhibition could not be mimicked by the analog, nicotinamide. While equimolar concentrations of nitroglycerin produced less inhibition of superoxide anion generation in opsonized zymosan-activated neutrophils than that observed with nicorandil, nitroglycerin did not alter free-radical production in PMA-stimulated neutrophils. Glyburide, the ATP-sensitive potassium-channel blocker, did not reverse the action of nicorandil on neutrophils. Thus, nicorandil is a uniquely different nitrovasodilator with anti-free-radical and neutrophil-modulating properties.
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PMID:Anti-free-radical and neutrophil-modulating properties of the nitrovasodilator, nicorandil. 132 63

Nicorandil exhibits a protective effect in the vascular system, which is thought to be due to vasodilatation from opening ATP-dependent potassium channels and donation of nitric oxide. Recently, nicorandil was shown to be renoprotective in models of acute kidney injury and glomerulonephritis. However, the specific mechanisms of renoprotection are unclear. We evaluated the effect of nicorandil on the rat remnant kidney model of chronic kidney disease. Blood pressure was unchanged by a 10-wk course of nicorandil, while albuminuria was significantly reduced. Glomerular injury and tubulointerstitial injury were also ameliorated by nicorandil. Oxidative stress, as noted by renal nitrotyrosine level and urine 8-hydroxy-2'-deoxyguanosine, were elevated in this model and was significantly reduced by nicorandil treatment. Treatment was associated with maintenance of the mitochondrial antioxidant, manganese SOD, in podocytes and with suppression of xanthine oxidase expression in infiltrating macrophages. Interestingly, these two cell types express sulfonylurea receptor 2 (SUR2), a binding site of nicorandil in the ATP-dependent K channel. Consistently, we found that stimulating SUR2 with nicorandil prevented angiotensin II-mediated upregulation of xanthine oxidase in the cultured macrophage, while xanthine oxidase expression was rather induced by blocking SUR2 with glibenclamide. In conclusion, nicorandil reduces albuminuria and ameliorates renal injury by blocking oxidative stress in chronic kidney disease.
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PMID:Nicorandil, a K(atp) channel opener, alleviates chronic renal injury by targeting podocytes and macrophages. 2262 55

Rapamycin is an immunosuppressive agent that is added to drug eluting stents. It prevents restenosis, but it also impairs reendothelialization. Nicorandil is a hybrid agent with adenosine triphosphated (ATP)-sensitive K+ (KATP) channel opener and nitrate properties. It prevents oxidative stress and cell apoptosis induced by rapamycin in endothelial cells in vitro. However, whether nicorandil promotes reendothelialization after angioplasty delayed by rapamycin remains to be determined. Balloon injury model was established in SD rats. Nicorandil increased reendothelialization impaired by rapamycin, and it decreased xanthine oxidase (XO)-generated reactive oxygen species (ROS) induced by rapamycin. In addition, eNOS expression inhibited by rapamycin was increased by nicorandil in vivo. In vitro, rapamycin-impeded cardiac microvascular endothelial cells (CMECs) migration, proliferation and rapamycin-induced ROS production were reversed by nicorandil. Knockdown of XO partially inhibited rapamycin-induced ROS production and cell apoptosis in CMECs, and it promoted CMECs migration and proliferation suppressed by rapamycin. Knockdown of Akt partially prevents eNOS upregulation promoted by nicorandil. The beneficial effect of nicorandil is exhibited by inhibiting XO and up-regulating Akt pathway. Nicorandil combined with rapamycin in effect rescue the deficiencies of rapamycin alone in arterial healing after angioplasty.
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PMID:Delayed reendothelialization with rapamycin is rescued by the addition of nicorandil in balloon-injured rat carotid arteries. 2771 57