Background: Diabetes is a metabolic condition characterized by chronic hyperglycemia and oxidative stress, which can cause organ damage. Bioactive chemicals have medical features such as antidiabetic and antioxidant capabilities, helping to avoid chronic disease by regulating physiological processes and improving metabolism and immunity. Aim: The current study aims to determine whether biocompatible chitosan nanoparticles are a natural adjuvant antidiabetic therapy with potential benefits, as well as to provide a systemic, quantifiable estimate of their effects on glycemic control, organ protection, and oxidative stress in a diabetic rat model. Methods: In rats, hyperglycemia was induced by a single intraperitoneal injection of alloxan monohydrate (120 mg/kg). Diabetic rats were given chitosan nanoparticles (300 mg/kg BW) orally for six weeks. The nanoparticles were studied with transmission electron microscopy (TEM), zeta potential, and FTIR spectroscopy. Biochemical, oxidative stress, histological, and immunohistochemical tests were performed. Results: Chitosan nanoparticles had a positive zeta potential (+47.7 mV) and distinct FTIR absorption bands. Treatment increased insulin levels by 65.15 percent and decreased blood glucose by 46 percent. The levels of glycosylated hemoglobin and amylase have been corrected. Liver enzymes (AST, ALP, and bilirubin) returned to near-normal values. The lipid profile improved with reductions in total cholesterol (↓40%), LDL-C (↓46.5%), and triglycerides (↓33.7%), while HDL-C increased (↑40%). CNPs reduced hepatic malondialdehyde by 19.4% and increased antioxidant enzyme activity (SOD by 49.3% and GST by 56.4%). Vitamin C, E, and glutathione levels were all partially restored. A histological examination revealed that chitosan nanoparticles preserved the normal structure of the liver and pancreas, remarkably reduced diabetic-induced damage, restored hepatocyte and islet morphology, and alleviated inflammation, necrosis, and β-cell atrophy compared to untreated diabetic rats. As regards immunostaining, chitosan nanoparticles retained strong insulin-positive immunoreactivity of pancreatic β-cells, enhancing β-cell expression in diabetic rats and reducing necrosis relative to poor staining in untreated diabetic animals. Conclusion: Chitosan nanoparticles have anti-diabetic, antioxidant, and tissue-protective properties, indicating their promise as a natural treatment for diabetes. Additional clinical trials are recommended to validate their safety and efficacy in humans.
Keywords | Alloxan, β-cells, Chitosan nanoparticles, Diabetes mellitus, Histopathology, Immunohistochemistry, Insulin, Nanotechnology, TEM