ArticlePharmacology research & perspectives2026
Morphological and Biochemical Insights Into the Renoprotective Effects of Combined N-Acetylcysteine and Glycine Treatment in Experimental Diabetic Nephropathy.
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Abstract
Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease. Oxidative stress and inflammation are central drivers of DN progression, yet no effective therapies exist to prevent or delay renal injury. This study investigated the renoprotective effects of glycine (GLY), N-acetylcysteine (NAC), and their combination administered at early versus late stages of streptozotocin induced diabetes. Forty-eight male Wistar rats (n = 48) were allocated into five groups: healthy controls (Group 1, n = 6), untreated diabetic rats (Group 2, n = 6), and three treatment groups (Groups 3-5, each n = 12). Diabetes was induced by a single intraperitoneal streptozotocin injection (55 mg/kg). Group 3 received NAC (100 mg/kg), Group 4 received GLY (250 mg/kg), and Group 5 received NAC + GLY. Each treatment group was subdivided into early (6 week, n = 6) and late (12 week, n = 6) intervention subgroups. Treatments were administered orally. Renal tissue was evaluated using classic histology, geometric morphometric analysis, and biochemical assays of superoxide dismutase (SOD) and myeloperoxidase (MPO). Statistical analyzes were performed using ANOVA with appropriate post hoc tests (p < 0.05). Untreated diabetic rats (Group 2) showed significantly decreased SOD activity, increased MPO levels, marked mesangial matrix expansion, glomerular hypercellularity, tubular epithelial degeneration, and interstitial inflammation with fibrosis. NAC (Group 3) and GLY (Group 4) each improved oxidative stress markers and partially restored glomerular and tubular morphology, with early treatment subgroups exhibiting more substantial benefit than late subgroups. The combined NAC + GLY therapy (Group 5) demonstrated the strongest renoprotective effect, preserving renal structure and biochemical parameters closest to healthy controls. To conclude, early combined administration of glycine and N-acetylcysteine yields superior protection against diabetes-induced renal injury compared with individual treatments. These findings support the therapeutic potential of antioxidant-amino acid combinations in preventing or delaying diabetic nephropathy.
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