Antioxidant action of xanthine oxidase inhibitor febuxostat protects the liver and blood vasculature in SHRSP5/Dmcr rats.

IF 2 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Journal of applied biomedicine Pub Date : 2023-06-01 DOI:10.32725/jab.2023.009

Mai Kakimoto, Moe Fujii, Ikumi Sato, Koki Honma, Hinako Nakayama, Sora Kirihara, Taketo Fukuoka, Shang Ran, Satoshi Hirohata, Kazuya Kitamori, Shusei Yamamoto, Shogo Watanabe

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引用次数: 2

Abstract

Background: Xanthine oxidase (XO) generates reactive oxygen species during uric acid production. Therefore, XO inhibitors, which suppress oxidative stress, may effectively treat non-alcoholic steatohepatitis (NASH) and atherosclerosis via uric acid reduction. In this study, we examined the antioxidant effect of the XO inhibitor febuxostat on NASH and atherosclerosis in stroke-prone spontaneously hypertensive 5 (SHRSP5/Dmcr) rats.

Methods: SHRSP5/Dmcr rats were divided into three groups: SHRSP5/Dmcr + high-fat and high-cholesterol (HFC) diet [control group, n = 5], SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) [fructose group, n = 5], and SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) + febuxostat (1.0 mg/kg/day) [febuxostat group, n = 5]. Glucose and insulin resistance, blood biochemistry, histopathological staining, endothelial function, and oxidative stress markers were evaluated.

Results: Febuxostat reduced the plasma uric acid levels. Oxidative stress-related genes were downregulated, whereas antioxidant factor-related genes were upregulated in the febuxostat group compared with those in the fructose group. Febuxostat also ameliorated inflammation, fibrosis, and lipid accumulation in the liver. Mesenteric lipid deposition decreased in the arteries, and aortic endothelial function improved in the febuxostat group.

Conclusions: Overall, the XO inhibitor febuxostat exerted protective effects against NASH and atherosclerosis in SHRSP5/Dmcr rats.

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黄嘌呤氧化酶抑制剂非布司他的抗氧化作用对SHRSP5/Dmcr大鼠肝脏和血管有保护作用。

背景:黄嘌呤氧化酶(XO)在尿酸生成过程中产生活性氧。因此，抑制氧化应激的XO抑制剂可能通过降低尿酸有效治疗非酒精性脂肪性肝炎(NASH)和动脉粥样硬化。在本研究中，我们检测了XO抑制剂非布司他对卒中易发自发性高血压5 (SHRSP5/Dmcr)大鼠NASH和动脉粥样硬化的抗氧化作用。方法:将SHRSP5/Dmcr大鼠分为3组:SHRSP5/Dmcr +高脂高胆固醇(HFC)饮食[对照组，n = 5]、SHRSP5/Dmcr + HFC饮食+ 10%果糖(40 ml/d)[果糖组，n = 5]、SHRSP5/Dmcr + HFC饮食+ 10%果糖(40 ml/d) +非布索他(1.0 mg/kg/d)[非布索他组，n = 5]。评估葡萄糖和胰岛素抵抗、血液生化、组织病理学染色、内皮功能和氧化应激标志物。结果:非布司他降低血浆尿酸水平。与果糖组相比，非布司他组的氧化应激相关基因被下调，而抗氧化因子相关基因被上调。非布司他还能改善肝脏的炎症、纤维化和脂质积累。非布司他组动脉肠系膜脂质沉积减少，主动脉内皮功能改善。结论:总体而言，XO抑制剂非布司他对SHRSP5/Dmcr大鼠NASH和动脉粥样硬化具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of applied biomedicine PHARMACOLOGY & PHARMACY-

CiteScore

2.40

自引率

7.70%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Applied Biomedicine promotes translation of basic biomedical research into clinical investigation, conversion of clinical evidence into practice in all medical fields, and publication of new ideas for conquering human health problems across disciplines. Providing a unique perspective, this international journal publishes peer-reviewed original papers and reviews offering a sensible transfer of basic research to applied clinical medicine. Journal of Applied Biomedicine covers the latest developments in various fields of biomedicine with special attention to cardiology and cardiovascular diseases, genetics, immunology, environmental health, toxicology, neurology and oncology as well as multidisciplinary studies. The views of experts on current advances in nanotechnology and molecular/cell biology will be also considered for publication as long as they have a direct clinical impact on human health. The journal does not accept basic science research or research without significant clinical implications. Manuscripts with innovative ideas and approaches that bridge different fields and show clear perspectives for clinical applications are considered with top priority.