Prospective Protective Effect of Ellagic Acid as a SIRT1 Activator in Iron Oxide Nanoparticle-Induced Renal Damage in Ra

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Prospective Protective Effect of Ellagic Acid as a SIRT1 Activator in Iron Oxide Nanoparticle-Induced Renal Damage in Rats Eman Taha Mohammed 1

&

Khalid S. Hashem 1

&

Ahmed Z. Abdelazem 2

&

Fatma A. M. A. Foda 2

Received: 17 December 2019 / Accepted: 4 January 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Despite the wide application of iron oxide nanoparticles (IONPs), little is known about the specific mechanism of their nephrotoxic effect. We aimed to evaluate the nephrotoxic effects of iron oxide nanoparticles (IONPs) in vivo and the protective effect of ellagic acid (EA) as a silent information regulator sirtuin 1 (SIRT1) activator against the induced nephrotoxicity. Forty male albino Wistar rats were randomly distributed into four equal groups (10 rats each): the control group (oral saline for 30 days), ellagic acid (EA) group (10 mg/kg b.w. EA, orally for 30 days), IONP group (20 mg/kg b.w. IONP I/P injection 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 antiapoptotic effects of 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. These results were confirmed by the improved histopathological renal features with EA administration. In conclusion, the present study provides the first evidence for the usefulness of EA as a sirtuin1 activator in the prevention or treatment of renal damage. Thus, EA could be used as a promising therapy for the prevention of IONP-induced nephrotoxicity. Keywords Ellagic acid . Iron oxide nanoparticles . SIRT1 . FOXO1 . KIAP . Nephrotoxicity

Introduction The field of nanotechnology has become an emerging threat to human life [1]. Nano-scale materials (with dimensions of 1– 100 nm) can move freely into the human and animal bodies via different routes of entry. NPs are circulated to the liver,

* Eman Taha Mohammed [email protected] Khalid S. Hashem [email protected] Ahmed Z. Abdelazem [email protected] Fatma A. M. A. Foda [email protected] 1

Department of Biochemistry, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt

2

Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt

spleen, lungs, heart, gastrointestinal tract, and brain after oral exposure or through inhalation [2]. Therefore, the distress about the toxicity of nanoparticles to humans and the environment has been eminent to researchers and still needs clarification. Recently, iron oxide nanoparticles (IONPs) have been wide