الفهرس 
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Abstract
Despite of the wide application of iron oxide nano-particles (IONPs), but the specific mechanism of their nephrotoxic effect need more investigations. Current study aimed to evaluate the nephrotoxic effects of iron oxide nano-particles (IONPs) in vivo and the protective effect of Sitagliptin (SG) and Ellagic acid (EA) as a silent information regulator sirtuin 1 (SIRT1) activator against the induced nephrotoxicity. Sixty male albino Wistar rats were randomly distributed into six equal groups (10 rats each): the control group (oral saline for 30 days), sitagliptin (SG) group (5 mg\kg b.w SG, orally for 30 days), Ellagic acid (EA) group (10mg/kg b.w EA, orally for 30 days), IONP group (20mg / kg b.w IONPs I/P injection at the 24th–30th day), SG + IONP group (5 mg/kg b.w /day SG for 30 days + 20 mg/kg b.w IONPs at the 24th–30th day) and EA + IONP group (10 mg/kg b.w/day EA for 30 days + 20 mg/kg b.w IONPs at the 24th–30th day). In the present study, the potent antioxidant and anti-apoptotic effects of SG and EA were indicated by the significant overexpression of SIRT1 in renal tissues that leads to significant decreases in renal MDA content, p53 protein level and forkhead-box transcription factor1 (FOXO1) expression, and significant increases in renal GSH level, catalase activity, growth arrest and DNA damage-inducible protein 45 alpha (GADDα45), and renal inhibition of apoptosis protein (KIAP)gene expression levels in the EA+IONP-treated group and SG+IONP-treated group. These results were confirmed by the improved histopathological renal features with SG and EA administrations. In conclusion, the present study provides the first evidence for the usefulness of SG and EA as sirtuin1 activators in the prevention or treatment of renal damage. Thus, SG and EA could be used as promising therapies for the prevention of IONP-induced nephrotoxicity.