دورية أكاديمية
Impact of Lesinurad and allopurinol on experimental Hyperuricemia in mice: biochemical, molecular and Immunohistochemical study
العنوان: | Impact of Lesinurad and allopurinol on experimental Hyperuricemia in mice: biochemical, molecular and Immunohistochemical study |
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المؤلفون: | Youssef Saeed Alghamdi, Mohamed Mohamed Soliman, Mohamed Abdo Nassan |
المصدر: | BMC Pharmacology and Toxicology, Vol 21, Iss 1, Pp 1-12 (2020) |
بيانات النشر: | BMC, 2020. |
سنة النشر: | 2020 |
المجموعة: | LCC:Therapeutics. Pharmacology LCC:Toxicology. Poisons |
مصطلحات موضوعية: | Lesinurad, Ameliorative effects, Hyperuricemia, Gene expression, Kidney affection, XOD activity, Therapeutics. Pharmacology, RM1-950, Toxicology. Poisons, RA1190-1270 |
الوصف: | Abstract 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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2050-6511 |
Relation: | https://doaj.org/toc/2050-6511 |
DOI: | 10.1186/s40360-020-0386-7 |
URL الوصول: | https://doaj.org/article/6b8569be0b054a9b8b36c2b616a8ea48 |
رقم الأكسشن: | edsdoj.6b8569be0b054a9b8b36c2b616a8ea48 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 20506511 |
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DOI: | 10.1186/s40360-020-0386-7 |