Vitamin D3 potentiates the nephroprotective effects of metformin in a rat model of metabolic syndrome: role of AMPK/SIRT1 activation and DPP-4 inhibition
| Autor: | Mohamed Abdel-Aal, Rasha H. Abdelghany, Nehal S. Wahba, Amira E Alsemeh, Salah A. Ghareib |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Vitamin endocrine system diseases Physiology Rat model AMP-Activated Protein Kinases 030204 cardiovascular system & hematology Pharmacology Nephropathy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) medicine Animals Dipeptidyl peptidase-4 Cholecalciferol Metabolic Syndrome Dipeptidyl-Peptidase IV Inhibitors business.industry nutritional and metabolic diseases AMPK General Medicine medicine.disease Metformin Rats 030104 developmental biology chemistry Metabolic syndrome business medicine.drug |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 99:685-697 |
| ISSN: | 1205-7541 0008-4212 |
| Popis: | The current study aimed to investigate the molecular mechanisms of metformin and vitamin D3-induced nephroprotection in a metabolic syndrome (MetS) rat model, evaluating the capacity of vitamin D3 to potentiate metformin action. MetS was induced by 10% fructose in drinking water and 3% salt in the diet. After 6 weeks, serum lipid profile and uric acid were measured, an oral glucose tolerance test (OGTT) was performed, and kidney function was investigated. In conjunction with the same concentrations of fructose and salt feeding, MetS rats with significant weight gain, dyslipidemia, hyperuricemia, and dysglycemia were treated orally with metformin (200 mg/kg), vitamin D3 (10 µg/kg), or both daily for 6 weeks. At the end of the study period, anthropometrical parameters were recorded, OGTT was reperformed, urine and blood samples were collected, and tissue samples were harvested at sacrifice. MetS rats showed dramatically declined renal function, enhanced intrarenal oxidative stress and inflammation, and extravagant renal histopathological damage with interstitial fibrosis. Metformin and vitamin D3 significantly reversed all the aforementioned deleterious effects in MetS rats. The study has verified the nephroprotective effects of metformin and vitamin D3 in MetS, accentuating the critical role of AMP-activated protein kinase/sirtuin-1 activation and dipeptidyl peptidase-4 inhibition. Given the synergistic effects of the combination, vitamin D3 is worth being investigated as an additional therapeutic agent for preventing MetS-induced nephropathy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|