黄嘌呤氧化酶抑制剂非布司他的抗氧化作用可保护 SHRSP5/Dmcr 大鼠的肝脏和血管系统。
Antioxidant action of xanthine oxidase inhibitor febuxostat protects the liver and blood vasculature in SHRSP5/Dmcr rats.
机构信息
Okayama University, Graduate School of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
Okayama University, Faculty of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.
出版信息
J Appl Biomed. 2023 Jun;21(2):80-90. doi: 10.32725/jab.2023.009. Epub 2023 May 22.
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.
背景
黄嘌呤氧化酶（XO）在尿酸生成过程中产生活性氧。因此，通过降低尿酸，抑制氧化应激的 XO 抑制剂可能通过尿酸降低有效治疗非酒精性脂肪性肝炎（NASH）和动脉粥样硬化。在这项研究中，我们研究了 XO 抑制剂非布司他对自发性高血压 5 型卒中易发性大鼠（SHRSP5/Dmcr）NASH 和动脉粥样硬化的抗氧化作用。
方法
SHRSP5/Dmcr 大鼠分为三组：SHRSP5/Dmcr+高脂肪高胆固醇（HFC）饮食（对照组，n = 5）、SHRSP5/Dmcr+HFC 饮食+10%果糖（40 ml/天）（果糖组，n = 5）和 SHRSP5/Dmcr+HFC 饮食+10%果糖（40 ml/天）+非布司他（1.0 mg/kg/天）（非布司他组，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
与果糖组相比，非布司他降低了血浆尿酸水平。非布司他组与果糖组相比，氧化应激相关基因下调，抗氧化因子相关基因上调。非布司他还改善了肝脏的炎症、纤维化和脂质堆积。动脉中肠系膜脂质沉积减少，主动脉内皮功能改善。
结论
总之，XO 抑制剂非布司他对 SHRSP5/Dmcr 大鼠的 NASH 和动脉粥样硬化具有保护作用。
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