Benzbromarone Attenuates Oxidative Stress in Angiotensin II‐ and Salt‐Induced Hypertensive Model Rats

Muraya, Nanako; Kadowaki, Daisuke; Miyamura, Shigeyuki; Kitamura, Kenichiro; Uchimura, Kohei; Narita, Yuki; Miyamoto, Yohei; Chuang, Victor Tuan Giam; Taguchi, Kazuaki; Maruyama, Toru; Otagiri, Masaki; Hirata, Sumio

doi:10.1155/2018/7635274

Cited by 20 publications

(11 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ang II was utilized to induce hypertension accompanied with vascular remodeling, oxidative stress, and inflammation [35][36][37][38], which is a better animal model of human essential hypertension [39]. The WT and FNDC5 -/mice were subjected to subcutaneous infusion of saline or Ang II (400 ng/kg/min for 2 weeks) with an osmotic minipump (ALZET 1002, Durect Corporation, Mountain View, CA, USA) [39].…”

Section: Mouse Model Of Hypertensionmentioning

confidence: 99%

FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway

Zhou

Qiu

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Vascular oxidative stress and inflammation play a major role in vascular diseases. This study was aimed at determining the protective roles of fibronectin type III domain-containing 5 (FNDC5) in angiotensin II- (Ang II-) induced vascular oxidative stress and inflammation and underlying mechanisms. Wild-type (WT) and FNDC5-/- mice, primary mouse vascular smooth muscle cells (VSMCs), and the rat aortic smooth muscle cell line (A7R5) were used in the present study. Subcutaneous infusion of Ang II caused more serious hypertension, vascular remodeling, oxidative stress, NLRP3 inflammasome activation, AMPK phosphorylation inhibition, and SIRT1 downregulation in the aorta of FNDC5-/- mice than those of WT mice. Exogenous FNDC5 attenuated Ang II-induced superoxide generation, NADPH oxidase 2 (NOX2) and NLRP3 upregulation, mature caspase-1, and interleukin-1β (IL-1β) production in A7R5 cells. The protective roles of FNDC5 were prevented by SIRT-1 inhibitor EX527, AMPK inhibitor compound C, or integrin receptor inhibitor GLPG0187. FNDC5 attenuated the Ang II-induced inhibition in SIRT1 activity, SIRT1 protein expression, and AMPKα phosphorylation in A7R5 cells, which were prevented by compound C, EX527, and GLPG0187. FNDC5 deficiency deteriorated Ang II-induced oxidative stress, NLRP3 inflammasome activation, AMPK phosphorylation inhibition, and SIRT1 downregulation in primary aortic VSMCs of mice, which were prevented by exogenous FNDC5. These results indicate that FNDC5 deficiency aggravates while exogenous FNDC5 alleviates the Ang II-induced vascular oxidative stress and NLRP3 inflammasome activation via the AMPK-SIRT1 signal pathway in VSMCs.

show abstract

Section: Mouse Model Of Hypertensionmentioning

confidence: 99%

FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway

Zhou

Qiu

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Benzbromarone is a kind of inhibiting renal tubular transporter URAT‐1 to promote uric acid excretion. In the process of ROS activation caused by high uric acid levels, benzbromarone can inhibit the activation of peroxides by reducing uric acid levels, thereby exerting an antioxidant effect (Huang et al, 2021; Muraya et al, 2018; Zhang et al, 2021). In summary, allopurinol and benzbromarone, as classic uric acid‐lowering drugs, can improve endothelial oxidative stress caused by high uric acid by reducing uric acid levels, thereby improving endothelial function and ED.…”

Section: Discussionmentioning

confidence: 99%

Hyperuricaemia is an important risk factor of the erectile dysfunction: A systematic review and meta‐analysis

et al. 2022

View full text Add to dashboard Cite

Serum uric acid can affect endothelial function, and hyperuricaemia‐induced endothelial dysfunction is involved in the pathogenesis of cardiovascular diseases. As endothelial dysfunction is also a main pathogenic mechanism of erectile dysfunction (ED), the present study aims to evaluate the relationship between hyperuricaemia and ED via systemic review and meta‐analysis. Five cohort studies and six cross‐sectional studies on hyperuricaemia and ED, including a total of 454,510 participants, were recruited. Odds ratio (OR) and the 95% confidence intervals (CI) were adopted to estimate the relationship between hyperuricaemia and ED. Overall risk on effects of urate‐lowering therapy (ULT) were analysed. In addition, subgroup analyses on study design, populations, age stratification and the object were conducted. In the patients with hyperuricaemia, the risk of ED was 1.59‐fold higher than (pooled OR = 1.59, 95% CI [1.29, 1.97]) the non‐hyperuricaemia counterparts. Urate‐lowing therapy (ULT) in these hyperuricaemia patients reduced the risk of ED by 27% (OR = 1.27, 95% CI [1.14, 1.41]). After subgroup analysis, the association between hyperuricaemia and ED remained significant apart from the >60 years subgroup. Hyperuricaemia is an important risk factor of ED, while ULT can reduce the risk of ED in hyperuricaemia. This study suggests that hyperuricaemia‐associated endothelial dysfunction may also underlie the pathogenesis of ED in these patients.

show abstract

“…Hence, since hyperuricemia and gout may be risk factors for dementia ( 5 , 46 ), the more potent effects of benzbromarone in reducing serum UA level and preventing acute gout attacks may explain the protective effect from incident dementia. A recent study by Muraya et al suggested that benzbromarone had direct antioxidant effects in vivo ( 56 ), and long-term use of antioxidant supplements can reduce the risk of dementia ( 57 , 58 ). Hence, this antioxidant effect can also explain why the use of benzbromarone was more effective in reducing incident dementia than other anti-gout preparations.…”

Section: Discussionmentioning

confidence: 99%

Association Between Use of Anti-gout Preparations and Dementia: Nested Case–Control Nationwide Population-Based Cohort Study

et al. 2021

View full text Add to dashboard Cite

Objectives: Gout is the most common form of inflammatory arthritis and was found to be independently associated with incident dementia in the elderly. However, the associations between anti-gout preparations and dementia were not well-studied.Methods: Data were collected from Taiwan's National Health Insurance Research Database (NHIRD). A 2005–2013 retrospective cohort study was conducted, and all investigated subjects were identified by International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Clinical Modification. Conditional logistic regression was used to evaluate the odds ratio of dementia in relation to different gout preparations (benzbromarone, allopurinol, sulfinpyrazone, probenecid) and number of days of anti-gout preparation use, after adjustment for potential confounding variables.Results: A total of 3,242 gout patients with and without dementia were selected from the NHIRD and included in the final analysis after 1:1 matching for age, gender, and diagnosis year of gout. In the anti-gout preparations, only use of Benzbromarone decreased the risk of dementia (adjusted OR, 0.81; 95% CI, 0.68–0.97). The result of the subgroup analysis revealed a trend toward a lower risk of dementia with longer use of benzbromarone. Use of benzbromarone for ≥180 days showed a significantly lower risk of dementia (adjusted OR, 0.72; 95% CI, 0.58–0.89). Moreover, the protective effect was more pronounced in males compared with females.Conclusion: This cohort study reveals that gout patients taking benzbromarone are at a decreased risk of developing incident dementia, especially with longer use and in male. Further prospective trials are warranted to confirm our findings.

show abstract

Benzbromarone Attenuates Oxidative Stress in Angiotensin II‐ and Salt‐Induced Hypertensive Model Rats

Cited by 20 publications

References 34 publications

FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway

FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway

Hyperuricaemia is an important risk factor of the erectile dysfunction: A systematic review and meta‐analysis

Association Between Use of Anti-gout Preparations and Dementia: Nested Case–Control Nationwide Population-Based Cohort Study

Contact Info

Product

Resources

About