title: The treatment of hyperuricemia.
abstract: Hyperuricemia has long been established as the major etiologic factor in gout. Alongside with an inflammatory state triggered by urate crystal deposition in the joints, hyperuricemia displayed additional pathophysiological consequences leading to tissue inflammation mainly in the vascular wall. Thus, therapeutic strategies used to treat hyperuricemia in the past decades have often been focused on limiting acute episodes. Recently, evidence has been accumulated suggesting that chronic urate deposition requires a correct treatment not limited to acute episodes based on the modulation of the activity of key enzymes involved in metabolism and excretion of urate including xanthine oxidoreductase (XO) and URAT1. The present review article will try to summarize the most recent evidences on the efficacy of XO inhibitors and uricosuric compounds in lowering uric acid levels in both the bloodstream and peripheral tissues. In particular, we will focus on the effect of novel XO inhibitors in counteracting uric acid overproduction. On the other hand, the effect of lowering uric acid levels via XO inhibition will be correlated with attenuation oxidative stress which leads to endothelial dysfunction thereby contributing to the pathophysiology of diabetes, hypertension, arteriosclerosis, and chronic heart failure. Hence, scavenging and prevention of the XO generated oxygen radical accumulation emerge as an intriguing novel treatment option to counteract uric acid-induced tissue damages.
authors: Institute of Research for Food Safety & Health (IRC-FSH), University "Magna Graecia" of Catanzaro, Italy.
authors: Micaela
authors: M
authors: Gliozzi
authors: Institute of Research for Food Safety & Health (IRC-FSH), University "Magna Graecia" of Catanzaro, Italy.
authors: Natalia
authors: N
authors: Malara
authors: Institute of Research for Food Safety & Health (IRC-FSH), University "Magna Graecia" of Catanzaro, Italy.
authors: Saverio
authors: S
authors: Muscoli
authors: Institute of Research for Food Safety & Health (IRC-FSH), University "Magna Graecia" of Catanzaro, Italy. Electronic address: mollace@libero.it.
authors: Vincenzo
authors: V
authors: Mollace
mesh_terms: D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects; D014527:Uric Acid / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D014527:Uric Acid; D014968:Xanthine Dehydrogenase
keywords: Hyperuricemia; Oxidative stress; Xanthine oxidase inhibitors