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Role of Uric Acid as an Endogenous Radical Scavenger and Antioxidant
Section snippets
SCAVENGER SYSTEMS IN GENERAL
Scavengers are characterized by the ability to rapidly inactivate radicals or oxidants without themselves being transformed into damaging products in the process. To be of functional relevance, they must also be present in amounts that ensure significant rates of reaction. Some of the biologically most important mediators of such reactions are enzymes (Table 2). Superoxide dismutases are specific for the dispropordonation of O2−, catalase degrades H2O2, and glutathione oxidases react with both H
IN VITRO EVIDENCE OF SCAVENGING BY URIC ACID
The activities of 3 different radical-generating systems in the absence and presence of uric acid were examined with the aid of luminol-enhanced chemiluminescence. The systems included (i) the formation of O2– radicals (together with H2O2) from allopurinol and O2 catalyzed by xanthine oxidase (XO),6, 11 (ii) the formation of OH radicals by an Fe2+-catalyzed disproportionation of H2O2 (Fenton reaction),12 and (iii) the oxidative burst reaction of human polymorphonuclear neutrophils (PMNs)
THE XANTHINE OXIDASE DILEMMA
At first sight, quenching of chemiluminescence by uric acid in the system containing XO may appear somewhat incongruous (see i in the preceding section). On the one hand, XO-catalyzed radical formation is held responsible for much of the reperfusion damage observed in vivo in tissues such as heart, brain, kidney, and intestine.2, 15, 16 On the other hand, with xanthine as substrate, XO will simultaneously produce the scavenger uric acid as the natural product. This dilemma can be resolved by
URIC ACID IN RELATION TO CORONARY ENDOTHELIAL FUNCTION
In the guinea pig heart it has been clearly demonstrated that the coronary endothelial cells are the site of uric acid formation.8 Also, in the human heart, the xanthine dehydrogenase activity is exclusively localized in the microvascular endothelium.18 This suggested to us that coronary vascular responses mediated by the endothelium could be in special need of protection from radicals and oxidants. Indeed, when isolated guinea pig hearts perfused with Krebs–Henseleit buffer were totally
THE SCAVENGER ROLE OF URIC ACID IN MAN
Uric acid is formed and released from the heart of several mammalian species (guinea pig, rat, dog) as the major purine product of adenine nucleotide catabolism.5 With respect to the human heart, however, there is controversy whether xanthine dehydrogenase is at all present. Several investigators have failed to detect enzyme activity,17, 21, 22 while others have reported its presence.18, 23, 24 In analyses conducted on paired samples of coronary sinus and arterial blood of patients who had
CONCLUSIONS
Because uric acid is present in high concentrations in plasma and seems particularly efficient at inactivating 2 very powerful oxidants, HO and HOC1, this substance can be assumed to act as a potent scavenger in vivo. Together with the other known scavenger systems, a protective screen against oxygen radicals and oxidants is therefore established under normal conditions. Since the scavengers are never totally suppressed or absent, the involvement of radicals in pathologic processes is difficult
ACKNOWLEDGMENTS
The authors thank Mr. W. Schrödl and Ms. D. Kiesl for technical assistance. Studies were supported in part by grants from the Friedrich Batir Foundation of the Medical Faculty, University of Munich.
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