الفهرس 
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Abstract
This study was intended to evaluate the antidiabetic effect of single or combined administration 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 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): healthy (G1), diabetic control (G2), ZnONPs treated (G3, 10 mg/kg b.wt), for Cr2O3NPs treated (G4, 1 mg/kg b.wt), SeNPs treated (G5, 0.4 mg/kg b.wt) and nanoparticles mixture treated (G6). The results displayed that diabetes significantly decreased body weight, serum insulin, C-peptide, adiponectin levels, erythrocyte glutathione peroxidase and serum superoxide dismutase activities, as well as high-density lipoprotein cholesterol, and total antioxidant capacity levels. While, it caused a substantial increase in serum glucose, glycosylated Hb, C-reactive protein, atherogenic index, HOMA–IR, malondialdehyde, lipid profile, interleukin-6 levels, liver and kidney functions parameters. Furthermore, the findings showed a decrease in hepatic insulin receptor substrate-1 (IRS-1) mRNA expression level and adipocyte peroxisome proliferator-activated receptor (PPAR-γ) mRNA expression level in type 2 diabetic rats. DNA damage was confirmed by performing the comet assay. Moreover, histological observation and measuring the lesion score of pancreatic and hepatic tissues were 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. These nanoparticles showed antidiabetic, anti-inflammatory, antioxidant, hypolipidemic, and antiapoptotic agents. The best mitigated antidiabetic effect was observed in the mixture administered group as it combined all previous synergetic mechanisms of each single compound.