Effects of Febuxostat on Oxidative Stress.
OBJECTIVE
We previously examined factors that affect the measured derivatives of reactive oxygen metabolites (d-ROMs), an indicator of reactive oxygen species production, and biological antioxidant potential (BAP), an indicator of antioxidant capacity, in typical health checkup examinees and reported the usefulness of measuring both indicators simultaneously. In addition, a positive correlation reportedly exists between d-ROMs and the visceral fat area measured by using computed tomography. A recent study of the relationship between uric acid levels and various obesity-related factors found that visceral fat was the factor most strongly related to uric acid levels. Uric acid is itself a potent endogenous antioxidant, but because reactive oxygen species are produced during uric acid generation, it is suggested that uric acid may have opposing effects. The objective of this study was to analyze the effect of febuxostat, a novel xanthine oxidase inhibitor, on oxidative stress.


METHODS
Study subjects were 43 hyperuricemia outpatients receiving care in the internal medicine department of our institution. The subjects were divided into a new administration group (29 patients) and a switched administration group (14 patients); the latter were allopurinol-treated patients with hyperuricemia who were switched to febuxostat. In addition to measuring the patients' uric acid and creatinine levels and estimated glomerular filtration rate before and after treatment, their d-ROMs and BAP as well as the BAP/d-ROMs ratio were also measured.


RESULTS
Both groups exhibited significant decreases in uric acid levels, as well as significant decreases in d-ROMs and BAP. No significant changes were observed in the BAP/dROMs ratio or renal function, including creatinine levels and estimated glomerular filtration rate.


CONCLUSIONS
Febuxostat could significantly reduce d-ROMs. However, BAP levels were also significantly reduced concurrently. No changes were observed in the BAP/d-ROMs ratios. This regulatory mechanism is believed to have counteracted changes in the in vivo oxidative stress balance caused by febuxostat administration.
Center for Preventive Medical Treatment, NTT West Takamatsu Hospital, Kagawa, Japan. Electronic address: ftoshi@kagawa.west.ntt.co.jp.
Toshiki
T
Fukui
Center for Preventive Medical Treatment, NTT West Takamatsu Hospital, Kagawa, Japan.
Mie
M
Maruyama
Center for Preventive Medical Treatment, NTT West Takamatsu Hospital, Kagawa, Japan.
Kazuhiro
K
Yamauchi
Center for Preventive Medical Treatment, NTT West Takamatsu Hospital, Kagawa, Japan.
Sumie
S
Yoshitaka
Center for Preventive Medical Treatment, NTT West Takamatsu Hospital, Kagawa, Japan.
Tadashi
T
Yasuda
Center for Preventive Medical Treatment, NTT West Takamatsu Hospital, Kagawa, Japan.
Youichi
Y
Abe
D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D000069465:Febuxostat / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006074:Gout Suppressants / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000097:blood*; D014527:Uric Acid / Q000097:blood*
D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D017382:Reactive Oxygen Species; D000069465:Febuxostat; D014527:Uric Acid; D000493:Allopurinol; D003404:Creatinine
BAP; d-ROMs; febuxostat; oxidative stress; uric acid; xanthine oxidase