BACKGROUND Hyperuricemia is an abnormal increase in uric acid levels in the blood. It is the cause of gout that manifested by inflammatory arthritis and painful disable. Therefore, current study evaluated the potential ameliorative impact of Lesinurad and Allopurinol on the kidneys of hyperuricemic mice at the biochemical, molecular and cellular levels. METHODS Lesinurad and allopurinol alone or in combination were orally administered to hyperuricemic and control mice for seven consecutive days. Levels of uric acid and blood urea nitrogen, along with antioxidants and inflammatory cytokines (IL-1β and TNF-α) were measured in the serum. The mRNA expression of mouse urate anion transporter-1, glucose transporter 9, organic anion transporters, in renal tissues were examined using quantitative real time PCR. Simultaneously, the immunoreactivity of transforming growth factor-beta 1 was examined immunohistochemically. RESULTS Lesinurad and allopurinol administration resulted in significant decrease in serum levels of uric acid, blood urea nitrogen, xanthine oxidase activity, catalase, glutathione peroxidase and inflammatory cytokines (IL-1β and TNF-α) reported in hyperuricemic mice. Both partially reversed oxonate-induced alterations in renal mURAT-1, mGLUT-9, mOAT-1 and mOAT-3 expressions, as well as alterations in the immunoreactivity of TGF- β1, resulting in the increase of renal uric acid secretion and excretion. The combined administration of lesinurad and ALP restored all altered parameters in a synergistic manner, improving renal function in the hyperuricemic mouse model employed. CONCLUSION This study confirmed synergistic ameliorative hypouricemic impact of both lesinurad and allopurinol in the treatment of hyperuricemia in mice at the biochemical, molecular and cellular levels.

中文翻译：

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Lesinurad和别嘌呤醇对小鼠实验性高尿酸血症的影响：生化，分子和免疫组化研究。

背景技术高尿酸血症是血液中尿酸水平的异常增加。这是痛风的原因，表现为炎症性关节炎和痛苦的残疾。因此，当前的研究在生物化学，分子和细胞水平上评估了莱辛纳德和别嘌呤醇对高尿酸血症小鼠肾脏的潜在改善作用。方法Lesinurad和别嘌呤醇单独或组合口服给高尿酸血症小鼠和对照组小鼠连续七天。测量血清中的尿酸和血尿素氮水平，以及抗氧化剂和炎性细胞因子（IL-1β和TNF-α）。使用定量实时PCR检测小鼠尿酸阴离子转运蛋白-1，葡萄糖转运蛋白9，有机阴离子转运蛋白在肾组织中的mRNA表达。同时，免疫组织化学法检测转化生长因子β1的免疫反应性。结果Lesinurad和别嘌呤醇的使用导致高尿酸血症小鼠的血清尿酸，血尿素氮，黄嘌呤氧化酶活性，过氧化氢酶，谷胱甘肽过氧化物酶和炎性细胞因子（IL-1β和TNF-α）水平显着降低。二者均部分逆转了含氧酸盐诱导的肾脏mURAT-1，mGLUT-9，mOAT-1和mOAT-3表达的改变，以及TGF-β1免疫反应性的改变，从而导致了肾脏尿酸分泌和排泄的增加。lesinurad和ALP的联合给药以协同方式恢复了所有改变的参数，改善了所用高尿酸血症小鼠模型的肾功能。