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Int Immunopharmacol ; 135: 112294, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38776856

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Metformin , MicroRNAs , PTEN Phosphohydrolase , Proto-Oncogene Proteins c-akt , Rats, Sprague-Dawley , Thioctic Acid , YAP-Signaling Proteins , Animals , Thioctic Acid/therapeutic use , Thioctic Acid/pharmacology , Metformin/pharmacology , Metformin/therapeutic use , Male , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , MicroRNAs/metabolism , MicroRNAs/genetics , 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 , 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
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