Abstract
Oxidative stress induced by hyperuricemia is closely associated with the renin-angiotensin system, as well as the onset and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). It is therefore important to reduce oxidative stress to treat hyperuricemia. We previously found that benzbromarone, a uricosuric agent, has a direct free radical scavenging effect in vitro. The antioxidant effects of benzbromarone were evaluated in vivo via oral administration of benzbromarone for 4 weeks to model rats with angiotensin II- and salt-induced hypertension. Benzbromarone did not alter plasma uric acid levels or blood pressure but significantly reduced the levels of advanced oxidation protein products, which are oxidative stress markers. Furthermore, dihydroethidium staining of the kidney revealed a reduction in oxidative stress after benzbromarone administration. These results suggest that benzbromarone has a direct antioxidant effect in vivo and great potential to prevent CVD and CKD.
Highlights
The activation of the renin-angiotensin system (RAS) is closely related to the progression and development of cardiovascular disease (CVD) and chronic kidney disease (CKD) [1, 2]
An increase in urinary protein and blood urea nitrogen (BUN) was observed in the benzbromarone and vehicle groups, there was no change in creatinine
The vehicle-treated group showed a significant increase in plasma concentrations of advanced oxidation protein products (AOPPs) after 2 weeks, in contrast to the olmesartan- and benzbromarone-treated groups, which showed a significant decrease in Advanced oxidation protein products (AOPPs) (Figure 2(a))
Summary
The activation of the renin-angiotensin system (RAS) is closely related to the progression and development of cardiovascular disease (CVD) and chronic kidney disease (CKD) [1, 2]. The intracellular uric acid activates NADPH oxidase, which produces ROS. Excess uric acid causes a vicious cycle by activating local RAS, which further increases oxidative stress [12]. We have previously shown that benzbromarone has a direct scavenging activity against superoxide radicals and reduces the levels of intracellular ROS produced by ANG II as well as uric acid in vascular endothelial cells [14]. The results were compared with those of model rats treated with olmesartan, an AT1 receptor blocker with antioxidant activity. These rats served as a positive control [18,19,20]
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