Comparative Evaluation of Metformin, PVP-Coated Silver Nanoparticles, and Metformin-Loaded PVP-Coated Silver Nanoparticles on Metabolic Dysfunction, Oxidative Stress, and Organ Injury in Experimental Diabetes
摘要
Diabetes mellitus is a multifactorial metabolic disorder characterized by persistent hyperglycemia, increased oxidative stress, and progressive damage to multiple organs. PVP-coated silver nanoparticles were synthesized using a chemical reduction approach in which silver nitrate was reduced in the presence of polyvinylpyrrolidone acting as a stabilizing and capping agent, followed by surface modification and drug loading. The resulting nanoparticles were comprehensively characterized using UV–visible spectroscopy, dynamic light scattering, zeta potential measurements, and FT-IR analysis to evaluate their optical properties, size distribution, surface charge, and functional group interactions. The effects of polyvinylpyrrolidone-coated silver nanoparticles (PVP-PVP-AgNPs), metformin (Met), and their combination on metabolic, biochemical, oxidative, and histopathological changes in an alloxan-induced diabetic rat model were evaluated. Adult male rats were allocated into control and diabetic groups and treated with Met, PVP-AgNPs, or their combination for four weeks. Induction of diabetes led to marked disturbances in glycemic control, lipid metabolism, liver and kidney function, hematological parameters, and oxidative stress markers. These biochemical changes were supported by histopathological findings showing significant structural damage in the liver, kidney, and pancreas. Met treatment improved glucose regulation, reduced oxidative stress, and partially restored organ function and tissue architecture. In contrast, rats treated with PVP-PVP-AgNPs showed impaired glycemic control, sustained oxidative stress, and signs of organ toxicity, particularly in the liver and kidneys. Although some lipid parameters appeared improved, these changes were likely related to alter hepatic function rather than true metabolic recovery. The combined treatment showed moderate protective effects, especially in reducing oxidative stress and improving tissue structure, but it did not fully normalize metabolic disturbances. Overall, the results recommend that oxidative stress is a key driver of diabetes-related complications. However, Met remains effective; PVP-PVP-AgNPs exhibit both beneficial and harmful effects, emphasizing the need for careful evaluation of nanoparticle-based therapies before their clinical use.