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Review Article |
Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (P.P.); Center for Integration of Medicine and Innovative Technology, Cambridge, Massachusetts (A.N.); Department of Surgery, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey (C.S.); and Department of Human Physiology and Clinical Experimental Research, Semmelweis University Medical School, Budapest, Hungary (C.S.)
Abstract
Abstract I. Introduction, Historical Background II. The Structure and Molecular Biochemistry of Xanthine Oxidoreductase III. Xanthine Oxidase-Derived Superoxide as Part of a Complex Oxidant and Antioxidant System IV. Xanthine Oxidase Inhibitors A. Allopurinol and Oxypurinol B. Novel Xanthine Oxidase Inhibitors V. Therapeutic Areas Relevant for Xanthine Oxidase Inhibitors A. Xanthine Oxidase Inhibitors in the Treatment of Gout and Tumor Lysis Syndrome B. Xanthine Oxidase and Ischemia-Reperfusion Injury 1. Xanthine Oxidase and Myocardial Ischemia-Reperfusion Injury. 2. Xanthine Oxidase and Stroke. 3. Xanthine Oxidase and Splanchnic Ischemia-Reperfusion. 4. Xanthine Oxidase and Ischemia-Reperfusion of Liver, Kidney, Lung, and Other Organs. C. Xanthine Oxidase and Circulatory Shock D. Xanthine Oxidase and Chronic Heart Failure E. Xanthine Oxidase and Vascular Disease: Hypertension, Hypercholesterolemia, Atherosclerosis, and Diabetes F. Xanthine Oxidase and Inflammatory Bowel Disease and Other Inflammatory Diseases G. Xanthine Oxidase and Various Forms of Toxic Organ Injury VI. Future Development of Xanthine Oxidase Inhibitors
The prototypical xanthine oxidase (XO) inhibitor allopurinol, has been the cornerstone of the clinical management of gout and conditions associated with hyperuricemia for several decades. More recent data indicate that XO also plays an important role in various forms of ischemic and other types of tissue and vascular injuries, inflammatory diseases, and chronic heart failure. Allopurinol and its active metabolite oxypurinol showed considerable promise in the treatment of these conditions both in experimental animals and in small-scale human clinical trials. Although some of the beneficial effects of these compounds may be unrelated to the inhibition of the XO, the encouraging findings rekindled significant interest in the development of additional, novel series of XO inhibitors for various therapeutic indications. Here we present a critical overview of the effects of XO inhibitors in various pathophysiological conditions and also review the various emerging therapeutic strategies offered by this approach.
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