دورية أكاديمية
Ameliorative effect of Metformin / alpha-lipoic acid combination on diabetic nephropathy via modulation of YAP/ miR-29a/PTEN/p-AKT axis.
| العنوان: | Ameliorative effect of Metformin / alpha-lipoic acid combination on diabetic nephropathy via modulation of YAP/ miR-29a/PTEN/p-AKT axis. |
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| المؤلفون: | Helmy SA; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura post code: 35516, Egypt. Electronic address: saharabdelgawad@mans.edu.eg., Nour OA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura post code: 35516, Egypt., G Abd El Salam AS; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura post code: 35516, Egypt. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2024 Jun 30; Vol. 135, pp. 112294. Date of Electronic Publication: 2024 May 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Thioctic Acid*/therapeutic use , Thioctic Acid*/pharmacology , Metformin*/pharmacology , Metformin*/therapeutic use , Diabetic Nephropathies*/drug therapy , Diabetic Nephropathies*/metabolism , Diabetic Nephropathies*/pathology , MicroRNAs*/metabolism , MicroRNAs*/genetics , Rats, Sprague-Dawley* , PTEN Phosphohydrolase*/metabolism , PTEN Phosphohydrolase*/genetics , YAP-Signaling Proteins*/metabolism , Proto-Oncogene Proteins c-akt*/metabolism , Diabetes Mellitus, Experimental*/drug therapy , Diabetes Mellitus, Experimental*/metabolism, Animals ; Male ; Rats ; Signal Transduction/drug effects ; Kidney/drug effects ; Kidney/pathology ; Kidney/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Diet, High-Fat ; Drug Therapy, Combination ; Hypoglycemic Agents/therapeutic use ; Hypoglycemic Agents/pharmacology ; Streptozocin |
| مستخلص: | Diabetic nephropathy (DN) is the most frequent and serious complication of type 2 diabetes (T2DM). Lack of a precise remedy and socio-economic burden of DN patients implements searching about alternative therapies. This study aims to evaluate the possible beneficial effect of alpha-lipoic acid (α-LA) alone or in combination with metformin (Met) in ameliorating STZ/High fat diet (HFD)-induced DN. T2DM was induced via HFD administration for 15 weeks and single ip injection of STZ (35 mg/kg) at week 7. Male Sprague-Dawley rats were randomly grouped as follows: control group, STZ/HFD-induced DN, Met/T; daily treated with 150 mg/kg Met, α-LA/T group; daily treated with 100 mg/kg α-LA, and Met/T + α-LA/T group; daily treated with Met and α-LA at same doses. Administration of Met and α-LA succeeded in attenuating STZ/HFD-induced DN as manifested by significant decrease in kidney weight as well as renal and cardiac hypertrophy index. Moreover, Met and α-LA improved glycemic control, kidney functions and lipid profile as well as restored redox balance. Additionally, Met and α-LA administration significantly upregulated PTEN level accompanied by significant downregulation in renal p-AKT and miR-29a levels. Histopathologically, Met and α-LA administration mitigated STZ/HFD-induced histopathological alterations in kidney and heart. Moreover, immunohistochemical examination revealed a significant decrease in renal YAP, collagen I and Ki-67. Taken together, these observations revealed that Met and α-LA administration could protect against STZ/HFD-induced DN. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Alpha-lipoic acid; Diabetic nephropathy; Ki-67; PTEN; YAP; miR-29a; p-Akt |
| المشرفين على المادة: | 73Y7P0K73Y (Thioctic Acid) 9100L32L2N (Metformin) 0 (MicroRNAs) EC 3.1.3.67 (PTEN Phosphohydrolase) 0 (YAP-Signaling Proteins) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 0 (MIRN29 microRNA, rat) EC 3.1.3.67 (Pten protein, rat) 0 (Yap1 protein, rat) 0 (Hypoglycemic Agents) 5W494URQ81 (Streptozocin) |
| تواريخ الأحداث: | Date Created: 20240522 Date Completed: 20240606 Latest Revision: 20240606 |
| رمز التحديث: | 20240607 |
| DOI: | 10.1016/j.intimp.2024.112294 |
| PMID: | 38776856 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2024.112294 |