Ameliorative effect of curcumin and/or cerium oxide nanoparticles on diabetes of rats: biochemical, molecular, and pathological insights

Diabetes mellitus encompasses a spectrum of metabolic dysfunctions fundamentally defined by a chronic state of hyperglycemia and oxidative cytotoxicity, where current therapies often fail to arrest progressive β-cell failure. This study evaluated the protective efficacy and mechanistic pathways of Nanocurcumin, Cerium Oxide Nanoparticles (CNPs), and their combinatorial formulation in alleviating pathologies in an alloxan-induced type 1 diabetic rat model. Nanoparticle characterization via transmission electron microscopy and XRD analysis confirmed the successful preparation of spheroidal Nanocurcumin (30 ± 5 nm) and CNPs (17 ± 2 nm). A total of fifty male albino rats were randomly allocated into five distinct experimental groups: negative control, diabetic (alloxan 150 mg/kg), Nanocurcumin (5 mg/kg), CNPs (45 mg/kg), and a combination group of both dosages. Intraperitoneal treatments were administered for three weeks pre-induction of diabetes and four weeks post-induction. Blood and tissue samples (liver and pancreas) were collected. The combination therapy demonstrated superior efficacy over monotherapies, reducing blood glucose by 69% and restoring serum insulin by 50%. It significantly ameliorated dyslipidemia, lowering total cholesterol by up to 50% and triglycerides by up to 56%, and attenuated hepatorenal injury, evidenced by reduced liver enzyme activities (ALT decreased by up to 36% and AST by up to 21%) alongside normalized urea and creatinine levels. In hepatic and pancreatic tissues, the treatments attenuated oxidative stress by reducing the lipid peroxidation marker MDA by 36-65% and enhancing antioxidant defenses, including increases in GSH (up to 58%), GPx (up to 25%), and catalase activities (up to 58%). Molecular analysis revealed upregulated hepatic IR, PI3K, and AKT expression, alongside suppression of pancreatic VEGF and iNOS. Histopathological examination confirmed islet architecture preservation and reduced NF-κB p65 immunoreactivity. Co-administration of Nanocurcumin and CNPs provides a potent, multi-targeted protective strategy, offering a promising preclinical avenue for diabetes management beyond traditional glycemic control, which warrants further translational investigation.