Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Nilvadipine (FK 235, FR 34235) suppressed ischemia (20 min)-reflow (20 min)-induced paw edema of mice (ED30:0.4 mg/kg i.v. and 2 mg/kg p.o.). Other calcium entry blockers of dihydropyridine-type also suppressed the edema, but 30-fold higher doses were required. 2. Oral dosing of nilvadipine suppressed carrageenan-induced paw edema (ED30:15 mg/kg in rats and 20 mg/kg in mice) at a potency corresponding to that of an anti-inflammatory drug, ibuprofen. Nifedipine, nicardipine and nimodipine resulted in a suppression of 30% only with 100 mg/kg oral dosing in rats. Nitrendipine, diltiazem and verapamil were without effect. 3. Nilvadipine inhibited superoxide radical (O-2production from xanthine oxidase (XOD) both with lactate dehydrogenase + NADH method and cytochrome c method (IC50:90 and 100 micrograms/ml, respectively). Nifedipine and nicardipine showed some inhibition, but the other calcium entry blockers failed to inhibit significantly even at 320 micrograms/ml. As uric acid formation was not reduced by the tested drugs, the inhibitory action might be due to their O-2scavenging effects. 4. Superoxide production of neutrophils from casein-induced peritoneal fluid in rats was most strongly inhibited by nilvadipine when the cells were stimulated by a calcium ionophore, A23187 (IC50:4 micrograms/ml). Inhibition by this drug when stimulated by f-methonyl-leucyl-phenylalanine and phorbol myristate acetate was less effective (IC50:20 and 30 micrograms/ml, respectively). Nifedipine and nicardipine inhibited neutrophil O-2production at higher concentrations (30-200 micrograms/ml) with all stimulants. Inhibitory actions by other drugs were weak. 5. Triggering of atherosclerosis depends largely on the oxidative stress on blood vessels after recently established concept.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition by nilvadipine of ischemic and carrageenan paw edema as well as of superoxide radical production from neutrophils and xanthine oxidase. 165 7

Oxidative stress is related to the progression of renal diseases and modulation of oxidative stress can lead to a reduction in vascular events in patients with chronic renal insufficiency (CRI). Indoxyl sulfate (IS) and xanthine oxidase (XO) are related to impaired neovasculogenesis in CRI. Hydralazine is suggested for blood pressure control in CRI. This study aimed to investigate whether hydralazine could improve ischemia-induced neovasculogenesis in CRI animals by reducing reactive oxygen species (ROS) levels. Mice underwent subtotal nephrectomy or sham surgery. Nitrendipine, probenecid, and allopurinol were used to reduce blood pressure, uric acid (UA), and XO activity levels, respectively, for comparison. Blood pressure, XO activity and UA levels that were increased after subtotal nephrectomy were reduced by hydralazine treatment. Allopurinol decreased blood XO activity and UA levels. Only hydralazine and allopurinol increased the number of circulating endothelial progenitor cells (EPCs) and improved neovasculogenesis in CRI mice. IS activated XO mRNA and ROS and inhibited the functions of EPCs and endothelial cells, which could be reversed by hydralazine. However, no additional beneficial effects were observed when XO was inhibited with both hydralazine and siRNA. In conclusion, hydralazine, as a potential XO inhibitor, not only reduced blood pressure and UA levels but also increased the number of circulating EPCs and improved neovasculogenesis in CRI animals. Hydralazine directly inhibited IS-induced ROS and XO activation in EPCs and endothelial cells, and restored their functions in vitro. Future studies should evaluate whether hydralazine could provide additional vascular protection in patients with CRI.
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PMID:Hydralazine improves ischemia-induced neovasculogenesis via xanthine-oxidase inhibition in chronic renal insufficiency. 3167 40