Allopurinol, an inhibitor of uric acid synthesis--can it be used for the treatment of metabolic syndrome and related disorders?
Allopurinol is an inhibitor of xanthine oxidoreductase (XOR) and inhibits the generation of uric acid (UA) as the final product of purine catabolism, as well as the resulting generation of superoxide (O2(-)), in humans. Elevation of the serum UA (SUA) level, referred to as hyperuricemia (HU), eventually leads to gout and allopurinol has been used for the treatment of HU and gout. Studies have revealed the role of elevated SUA levels and the associated oxidative stress (OS) in a broad spectrum of pathological conditions and it is anticipated that these findings would also expand the use of allopurinol as a therapeutic drug. This article presents a review of reports, mainly of recent studies, on the efficacy of allopurinol in various diseases and explores novel potential uses of the drug. Important novel and potential uses of great interest include metabolic syndrome (MetS) and related disorders, chronic kidney disease (CKD), nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Ischemia-reperfusion injury and mucositis, encountered as adverse effects of cancer treatment, have also been under investigation as potential targets for allopurinol.
Suzuki
Iwao
I
GlaxoSmithKline K.K., General Pharma Franchise, Tokyo, Japan. Iwao.Suzuki@gsk.com
Yamauchi
Takayuki
T
Onuma
Masahiro
M
Nozaki
Shigeo
S
D000493:Allopurinol / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005234:Fatty Liver / Q000188:drug therapy; D006801:Humans; D008107:Liver Diseases / Q000178:diet therapy; D024821:Metabolic Syndrome / Q000188:drug therapy*; D052016:Mucositis / Q000188:drug therapy; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy; D015427:Reperfusion Injury / Q000188:drug therapy; D014527:Uric Acid / Q000097:blood; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D014527:Uric Acid; D000493:Allopurinol; D014968:Xanthine Dehydrogenase