Docosahexaenoic acid (DHA), an omega-3 fatty acid, is widely recognized for its therapeutic benefits in various gastrointestinal disorders. This study aimed the renoprotective and metabolic effects of an oral formulation (DL formulation) containing DHA and the Dipeptidyl Peptidase-4 (DPP-4) inhibitor linagliptin in a rat modeinduced type 2 diabetes.

Male albino rats were divided into four groups: control (C), diabetic (D), diabetic treated with the DL formulation (DDL), and diabetic treated with insulin (DI). Tywas induced by a high-sucrose diet and confirmed by elevated blood glucose levels. After a 30-day treatment period, kidney and serum biochemical parameters were aHistopathological examination of kidney tissue was performed, and immunohistochemistry was used to measure insulin content in pancreatic islets. The study evaluatedglucose, glycated hemoglobin, plasma insulin, oxidative stress markers, and renal function indicators including proteinuria, enzymuria, creatinine, and uric acid. Additionaexpression of renal Caspase-9, NGAL, glucose transporters (GLUT-1), and polyol pathway enzyme activities were measured.

The DL formulation significantly reduced hyperglycemia and preserved kidney structure in diabetic rats, showing improved insulin levels, lipid profiles, and increrates. It also counteracted diabetes-induced increases in lipid peroxidation, enzymuria, creatinine, uric acid levels, and upregulated the renal renin-angiotensin system. Ntreatment with the DL formulation led to a normalization of the expression of renal Caspase-9, NGAL, and GLUT-4. These results demonstrate the antidiabetic and renopproperties of the DL formulation.

In conclusion, the DL formulation was effective in restoring metabolic balance and improving renal function in a sugar-rich diet-induced type 2 diabetes motreatment may serve as a promising alternative for managing diabetic-related kidney dysfunction and metabolic disorders. Further exploration of this therapy is warranteits potential in age-related and chronic diabetic conditions.