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

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 nicotinamide adenosine dinucleotide phosphate (NADPH): 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, glutathione concentration, and a significant decrease of inducible nitric oxide synthase mRNA expression and malondialdehyde concentration. In coordination, dopamine, serotonin concentrations, acetylcholinesterase, 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 the PPE administration. Conclusion: PPE is a potent antioxidant that can effectively increase the transcription of Nrf2 and NQO1 in TiO2 -NPs-induced brain toxicity