Mitigating effect of single or combined administration of nanoparticles of zinc oxide, chromium oxide, and selenium on genotoxicity and metabolic insult in fructose/streptozotocin diabetic rat model

This research was intended to evaluate the antidiabetic effect of single or combined administration of nanoparticles of zinc oxide nanoparticles (ZnONPs), chromium oxide nanoparticles (Cr₂O₃NPs), and selenium nanoparticles (SeNPs), on genetic and metabolic insult in fructose/streptozotocin diabetic rat model. Type 2 diabetes mellitus was induced by feeding sixty adult male albino rats with a high fructose diet accompanied by a single i.p. injection of streptozotocin (STZ). The rats were divided into 6 groups (10 rats/each) and the doses of nanoparticles were 10 mg/kg b.wt for ZnONPs, 1 mg/kg b.wt for Cr₂O₃, and 0.4 mg/kg b.wt for SeNPs. The results displayed that diabetes significantly decreased bodyweight, serum insulin, C-peptide, adiponectin levels, erythrocyte glutathione peroxidase, serum superoxide dismutase activities, high-density lipoprotein cholesterol (HDL-C), and total antioxidant capacity while causing a substantial increase in serum glucose, C-reactive protein, atherogenic index, HOMA–IR, malondialdehyde, lipid profile, interleukin-6 levels, and liver function and kidney function parameters. Furthermore, the findings showed a decrease in insulin receptor substrate-1 (IRS-1) hepatic mRNA expression level and peroxisome proliferator-activated receptor (PPAR-γ) adipocyte mRNA expression level in type 2 diabetic rats. DNA damage was confirmed by performing the comet assay. Moreover, histological observation of pancreatic and hepatic tissues was performed, which were consistent with the biochemical results. The present study confirmed that oral administration of ZnONPs, Cr₂O₃NPs, SeNPs, and their mixture improved all the biochemical and genetic parameters toward normal levels and ameliorated the diabetic consequences that were manifested by restricting cellular DNA damage which maintaining pancreatic and hepatic tissues from oxidative damage. The best reported antidiabetic effect was observed in the mixture administered group.