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Protective effect of Pomegranate Peel Extract against Titanium dioxide nanoparticles (TiO2- NPs) –induced neurotoxicity in rats

Mohamed Ahmed Kandeil,Eman Taha Mohammed,Khalid Shaban Hashem,Rawya Gaber Abd El-Wahab.

Abstract
Background: Although the wide applications of titanium dioxide nanoparticles (TiO2-NPs), little is known about their neurotoxic effects. The nuclear factor erythroid 2-related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. Nrf2 controls the expression of an array of antioxidant response enzymes such as NAD (P) H: quinone oxidoreductase 1 (NQO1).
Objectives: We aimed to study the effect of Pomegranate Peel Extract (PPE) on cerebral Nrf2/NQO1 signaling in TiO2-NPs-induced neurotoxicity.
Methods: Forty male albino rats were distributed into four groups (n=10): control group, TiO2-NPs group: rats received oral dose of TiO2-NPs (500 mg/kg/day) on the 17th- 30th days, PPE group: rats received PPE (200 mg/kg/day orally) for 30 days, and PPE+ TiO2-NPs group: rats received PPE an hour before TiO2-NPs administration with the same doses.
Results: The potent antioxidant effect of PPE was indicated by a significant increase of both Nrf2 and NQO1 mRNA expressions, GSH concentration and a significant decrease of INOS mRNA expression and MDA concentration. In coordination, dopamine, serotonin concentrations, acetyl cholinesterase and catalase activities returned back to normal. These results were confirmed by the histopathological findings which showed a severe degeneration, edema and congestion, extended in the brain tissue in TiO2-NPs and these features were improved with PPE administration.
Conclusion: PPE is a potent antioxidant that can effectively increase the transcription of Nrf2 and NQO1 in TiO2-NPs induced brain toxicity.

Key words: TiO2 nanoparticles, neurotoxicity, Nrf2, NQO1, pomegranate peel



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