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Abstract: SA-PO635

Evaluation of the Antioxidant Effects of Benzbromarone in Angiotensin II Induced Hypertension Model

Session Information

  • Pharmacology
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Kadowaki, Daisuke, Sojo University, Kumamoto, Japan
  • Narita, Yuki, School of Pharmacy, Kumamoto University, Kumamoto, Japan
  • Miyamura, Shigeyuki, Sojo University, Kumamoto, Japan
  • Uchimura, Kohei, Washington University in St. Louis, Saint Louis, Missouri, United States
  • Kitamura, Kenichiro, University of Yamanashi School of Medicine, Chuo, Yamanashi, Japan
  • Maruyama, Toru, School of Pharmacy, Kumamoto University, Kumamoto, Japan
  • Hirata, Sumio, School of Pharmacy, Kumamoto University, Kumamoto, Japan
  • Seo, Hakaru, Sojo University, Kumamoto, Japan
Background

Uric acid exerts an important antioxidant effect against external oxidative stress under physiological conditions. However, 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). Furthermore, uric acid locally activates the renin-angiotensin system, thus producing angiotensin II and subsequently increasing intracellular oxidative stress. Benzbromarone has been reported to suppress uric acid reabsorption via uric acid transporter 1 inhibition in renal tubular cells. In this study, we evaluated the antioxidant effect of benzbromarone from several perspectives in vitro and in vivo.

Methods

First, the direct radical-trapping capacity of benzbromarone was measured by chemiluminescence assay and electron paramagnetic resonance spectroscopy in vitro. Second, the intracellular antioxidant activity of benzbromarone was evaluated using endothelial cells. Finally, 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.

Results

benzbromarone showed direct radical scavenging capacity against the superoxide anion radical in vitro. In addition, benzbromarone inhibited reactive oxygen species production that was induced by angiotensin II or uric acid in endothelial cells. In in vivo study, 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.

Conclusion

These findings suggest that benzbromarone possesses the ability directly to scavenge radicals and may act as an antioxidant against uric acid and angiotensin II-induced oxidative stresses in endothelial cells or angiotensin II induced hypertension.