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)

Enhanced oxidant stress occurs under many pathophysiologic conditions (e.g., inflammation) and can be induced and mimicked by continuous nitrate therapy, eliciting increases in platelet activity, enhanced formation of reactive oxygen species (ROS), and impaired nitrate-induced vasorelaxation. Analysis was performed of effects of coinfusion of glycerol trinitrate (GTN) either with a carvedilol metabolite with antioxidant properties or with antioxidant vitamin C (Vit-C) on various hemodynamic parameters during enhanced oxidant stress associated with nitrate tolerance. Carvedilol metabolite (BM910228: 4.5 microg/kg/min) or Vit-C (55 microg/kg/min) was coadministered with GTN (1.5 microg/kg/min) for 5 days in chronically instrumented dogs. Changes in coronary diameters (CD) and other hemodynamic parameters were continuously monitored, as well as changes in platelet function. At the beginning of GTN treatment, CD increased by 9.8 +/- 0.4% and progressively declined to basal control values within 3 days. However, with additional antioxidant protection either with BM910228 or with Vit-C, the GTN-induced increase in CD was maintained (8.6 +/- 0.4% or 10.5 +/- 0.6%) and remained elevated for the entire infusion period. The thrombin-stimulated intracellular Ca2+ concentrations of platelets remained nearly unchanged during Vit-C or BM910228 in contrast to the increase with GTN. The basal cyclic guanosine monophosphate (cGMP) contents of platelets after GTN coadministered with BM910228 or with Vit-C increased on day 1 to 233 or to 250% versus control and remained at that level. Additional in vitro tests with xanthine oxidase-induced oxidant stress resulted in a more or less pronounced scavenging of O2- radicals by BM920228, Vit-C, or superoxide dismutase (SOD). Coadministration of carvedilol metabolite BM910228 or of Vit-C along with GTN suppressed noxious effects of GTN-induced oxidant stress such as increased platelet activity and impaired nitrate-induced vasorelaxation.
 ...
PMID:Tolerance to nitrates with enhanced radical formation suppressed by carvedilol. 1059 22

The cardioprotective properties of new pharmaceuticals such as carvedilol might be explained by enhanced mitochondrial protection. The aim of this work was to determine the role of carvedilol in the protection of heart mitochondria from oxidative damage induced by hypoxanthine/xanthine oxidase, a known source of oxidative stress in the vascular system. Carvedilol reduced oxidative-stress-induced mitochondrial injury, as seen by the delay in the loss of the mitochondrial transmembranar potential (Delta Psi), the decrease in mitochondrial swelling, and the increase in mitochondrial calcium uptake. Carvedilol improved the mitochondrial respiratory activity in state III and offered an overall protection in the respiratory control and in the P/O ratios in mitochondria under oxidative stress. The data indicated that carvedilol was able to partly protect heart mitochondria from oxidative stress-induced damage. Our results suggest that mitochondria can be important targets for some cardioprotective pharmaceuticals.
 ...
PMID:Carvedilol reduces mitochondrial damage induced by hypoxanthine/xanthine oxidase: relevance to hypoxia/reoxygenation injury. 1221 73

The cellular role of mitochondria includes ATP generation and the modulation of cytosolic calcium signals, besides being the "crossroads" for several cell death pathways. The maintenance of optimal mitochondrial functioning during the disease process increases the chances for survival. For example, ischaemia followed by reperfusion is known to negatively affect mitochondrial function, namely by inducing a deleterious condition called mitochondrial permeability transition (MPT). The MPT is responsible for mitochondrial dysfunction and can ultimately lead to cell death. Therefore, it seems important to protect mitochondrial function in cardiac disease. Carvedilol, a beta-adrenergic receptor antagonist with antioxidant properties, has a positive impact on cardiac mitochondria during in vitro, ex-vivo and in vivo models of cardiac dysfunction. Particularly, carvedilol was shown to inhibit MPT in isolated heart mitochondria and protect mitochondria against the oxidative damage induced by the xanthine oxidase/hypoxanthine pro-oxidant system. The observation that carvedilol acts as an inhibitor of mitochondrial complex-I is also of importance, since this mitochondrial system was proposed as cause of the cardiotoxicity associated with the anti-neoplasic drug doxorubicin. This review points out the major findings concerning the positive impact of carvedilol on mitochondrial function and its use in the treatment of myocardial diseases where oxidative stress is known to be involved.
 ...
PMID:Are the antioxidant properties of carvedilol important for the protection of cardiac mitochondria? 1585 34