Preclinical evaluation of silver-doped copper carbonate nanoparticles for antidiabetic and wound healing effects in...

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia and oxidative stress, leading to multi-organ dysfunction and impaired wound healing. This study evaluated the antidiabetic, antioxidant, hematological, biochemical, and wound-healing effects of silver-doped copper carbonate nanoparticles (Ag-CuCO₃ NPs) in alloxan-induced diabetic albino mice. Diabetes was induced via intraperitoneal injection of alloxan monohydrate (150 mg/kg) and animals were divided into control, diabetic control, and treatment groups receiving low dose (LD) or high dose (HD) of Ag-CuCO₃ NPs orally for 28 days. Hematological, biochemical, hormonal, electrolyte, and wound-healing parameters were assessed, and data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post hoc test, with p < 0.05 considered statistically significant. Diabetic controls showed severe hyperglycemia (> 280 mg/dL), elevated LDL (64 ± 3 mg/dL), reduced RBC count (5.1 ± 0.3 × 10⁶/µL) and delayed wound closure beyond Day 20. Low-dose Ag-CuCO₃ NP treatment significantly reduced fasting blood glucose levels from diabetic values (> 280 mg/dL) toward near-normal levels and improved hematological indices, including a ~ 42% increase in RBC count (2.85 to 4.05 × 10⁶/µL), ~ 38% increase in hemoglobin (7.46 to 10.33 g/dL), and ~ 115% increase in hematocrit (10.43 to 22.43%) compared with diabetic controls. Insulin levels increased by ~ 53% (6.12 to 9.35 µIU/mL), while sodium levels improved by ~ 3% (136.13 to 140.03 mmol/L), indicating partial restoration of metabolic and renal balance. High-dose treatment produced a more pronounced improvement in oxidative status, with SOD activity increasing by ~ 100% (2.31 to 4.62 U/mg protein) and lipid peroxidation marker MDA decreasing by ~ 51% (6.41 to 3.12 nmol/mg protein). However, high-dose treatment was also associated with elevations in hepatic enzymes, including AST (~ 50% increase; 56.33 to 84.66 U/L) and ALT (~ 114% increase; 25.66 to 55 U/L), suggesting potential dose-related hepatic stress. While high-dose treatment achieved faster glycemic and oxidative stress correction, low-dose treatment provided more balanced therapeutic efficacy with minimal biochemical disturbances. Overall, these findings provide preliminary evidence of dose-dependent antidiabetic, antioxidant and wound-healing effects of Ag-CuCO₃ nanoparticles in a preclinical diabetic model, warranting further mechanistic and comparative investigations.