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J.Health Sci., 50(6), 647-653, 2004
Potassium Bromate-Induced Hyperuricemia Stimulates Acute Kidney Damage and
Oxidative Stress
Satoshi Watanabe,* Yukie Tajima, Tomoko Yamaguchi, and Tetsuya Fukui
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo
142-8501, Japan
Acute exposure of mice to potassium bromate
(KBrO3), which is a major disinfection by-product of ozonation
and/or chlorination of bromide-containing raw waters, causes serious kidney failure and neuropathological
disorders. We observed significant elevations of serum uric acid levels and xanthine oxidase activity by
KBrO3 administration (1.2 mmol/kg) with elevating relative kidney weight, serum creatinine levels and renal oxidative stress.
Therefore, allopurinol was administered to
KBrO3-treated mice to examine if the elevation of blood uric acid levels causes
acute kidney damage and renal oxidative stress. These
KBrO3-induced elevations were significantly prevented by
intraperitoneal administration of allopurinol (10 or 50 mg/kg) and significant correlation between kidney damage
and uric acid levels was observed. Reduction of catalase activity in the kidney of
KBrO3-treated mice, which results in the accumulation of hydrogen peroxide, was also restored by allopurinol. There were significant correlations
between catalase activity and uric acid levels or kidney damage. Furthermore, in
in vitro experiment, catalase activity was reduced in the presence of physiological concentration of uric acid (approximately 0.3 mM or more). These
results suggest that the reduction of catalase activity by the elevation of blood uric acid levels is a major cause of
KBrO3-induced acute kidney damage. Allopurinol also suppressed
KBrO3-induced increases of renal thiobarbituric
acid reactive substances levels and renal protein carbonyl levels of mice. Furthermore, significant correlation
between oxidative stress and blood uric acid levels was observed. Therefore,
KBrO3 seems to cause hyperuricemic status which in turn brings about acute kidney damage and oxidative stress with reducing catalase activity.
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