Investigation of Protective Effects of Carvacrol and Hesperidin in Rats with Streptozotocin-Induced Diabetic Nephropathy

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Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia resulting from impaired insulin secretion or action. Persistent hyperglycemia contributes to the development of micro- and macrovascular complications, particularly affecting the kidneys and leading to diabetic nephropathy through mechanisms involving oxidative stress, fibrosis and apoptosis. Purpose: This study aimed to investigate the protective effects of hesperidin and carvacrol, individually and in combination, on streptozotocin-induced diabetic nephropathy in a Type 1 diabetes rat model. Study design: An experimental in vivo animal study was conducted using a streptozotocin-induced Type 1 diabetic rat model. Methods: Sixty adult Wistar Albino rats were randomly divided into six groups (n = 10): Control, Diabetes, Vehicle, Diabetes + Carvacrol, Diabetes + Hesperidin, and Diabetes + Hesperidin + Carvacrol. Following a 6-week (42-day) experimental period, systemic necropsy was performed. Renal tissues were evaluated histopathologically using Periodic Acid–Schiff, Masson’s trichrome, and Best Carmine staining. Immunohistochemical analyses were conducted to assess Bcl-2, Bax, Caspase-3, Caspase-9 expression, and apoptotic cell death using the TUNEL assay. Results: Histopathological analysis demonstrated significant differences in tubular dilatation, intracellular vacuolization, and mesangial matrix expansion among groups (p < 0.05), whereas tubular atrophy, hyaline accumulation, mononuclear cell infiltration, and the number of sclerotic glomeruli were not significantly different (p > 0.05). Treatment with hesperidin and carvacrol significantly attenuated renal injury and fibrosis in diabetic rats (p < 0.001). Diabetic kidneys exhibited increased immunopositivity for Bax, Caspase-3, and Caspase-9 and decreased Bcl-2 expression (p < 0.001). Combined hesperidin and carvacrol treatment markedly reduced apoptotic cell numbers compared with the untreated diabetic group (p < 0.001). Conclusions: The combined administration of hesperidin and carvacrol exerts protective effects against diabetic nephropathy, potentially through modulation of the Bcl-2/Bax-mediated apoptotic pathway and attenuation of renal fibrosis.