Potassium Bromate-Induced Hyperuricemia Stimulates Acute Kidney Damage and Oxidative Stress

Abstract

Acute exposure of mice to potassium bromate (KBrO 3 ), 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 KBrO 3 administration (1.2 mmol/kg) with elevating relative kidney weight, serum creatinine levels and renal oxidative stress. Therefore, allopurinol was administered to KBrO 3 -treated mice to examine if the elevation of blood uric acid levels causes acute kidney damage and renal oxidative stress. These KBrO 3 -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 KBrO 3 -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 KBrO 3 -induced acute kidney damage. Allopurinol also suppressed KBrO 3 -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, KBrO 3 seems to cause hyperuricemic status which in turn brings about acute kidney damage and oxidative stress with reducing catalase activity.

Influence of ethanolic extract of strawberry leaves for abrogating bromate hazards in male rats

“…This result is in agreement with Parsons and Chipman's report (Parsons & Chipman, 2000). Potassium bromate has the ability to cause tissue damage by the free radical mediated reactions Watanabe, Tajima, Yamaguchi, & Fukui, 2004) and by facilitating the production of free radicals which react with some cellular components and cause oxidation of polyunsaturated fatty acids which in turn cause lipid peroxidation (Abd El-Ghany & El-Metwally, 2010). Portion of potassium bromate may be excreted in urine as bromate or bromide (Fuji et al, 1982) which will lower its level in the blood and tissues.…”

Involvement of oxidative stress in patients of gout and antioxidant effect of allopurinol

“…[10,11] Association of hyperuricemia with hypertension, visceral obesity, type 2 diabetes, insulin resistance, renal diseases, and cardiovascular and cerebrovascular events can be explained on the basis of the results of this study. As hyperuricemia causes oxidative stress and interrelated trio of vascular inflammation, oxidative stress, and endothelial dysfunction, which lead to oxidative damage of lipids and proteins, is the principal cause in pathology of all the abovementioned conditions.…”

Protective influence of Carica papaya L. aqueous leaf extract against hyperuricemia and acute renal injury in a murine model

“…Uric acid elevation in this study appeared to be a response to KBrO 3 -induced oxidative stress, which may have eventually reduced catalase activity and increased xanthine oxidase activity leading to elevated BUA levels [6,10]. In this study, there was an attenuated increase in the BUA levels in the PLE-treated groups probably due to the xanthine oxidase inhibitory activity of one or more of its components [6,11].…”

“…Increased xanthine oxidase activity produces free radicals that further generate superoxide anions during the purine metabolism catalyzed by xanthine oxidase and accumulation of peroxynitrite [10,12]. Oxidative damage is one of the most important pathogenic mechanisms in the development of renal diseases by forming cellular injury such as inflammation, cell death, necrosis, and DNA damage.…”