Hesperidin Attenuates Titanium Dioxide Nanoparticle-Induced Neurotoxicity in Rats by Regulating Nrf-2/TNF-α Signaling Pathway, the Suppression of Oxidative Stress, and Inflammation
Amir Eid, Sherien S. Ghaleb, Amr R. Zaki, Marwa A. Ibrahim, Ahmed A. Farghali, Lamiaa E. Ali, Mohamed A. Abdelgawad, Mohammed M. Ghoneim, Rasha Hamed Al‐Serwi, Randa M. Hassan, Manar Ahmad
Abstract
High Resolution Image Download MS PowerPoint Slide Background: Titanium dioxide nanoparticles (TiO 2 NPs) are widely utilized and consumed mainly as food additives. Oxidative stress is considered to be the basic effect of TiO 2 NPs through biological interactions. Hesperidin (HSP) is a bioflavonoid (flavanone glycoside) with lipid-lowering, inflammation, oxidative stress suppression, antihypertensive, cancer-fighting, and antiedema effects. Objective: This study was to investigate the possible protective influences of HSP of subchronic oral TiO 2 NP exposure on the brains of rats, including neurotransmitters, oxidative stress/antioxidant parameters, inflammatory markers, and histological changes in the brains of adult male albino rats. Methodology: The experiment was executed on 80 albino rats. The animals were randomly divided into 4 equal groups. The first group served as a control; the second group was treated with oral doses of HSP (100 mg/kg Bw daily); the third group received TiO 2 NPs (200 mg/kg Bw orally daily); and the fourth group was treated with TiO 2 NPs and an oral dose of HSP daily for 8 weeks. Blood samples were obtained for biochemical analysis. Neurotransmitters, oxidative stress biomarker levels, and inflammatory markers were measured in brain homogenates. Histological examination of the brain was performed through H&E staining. Results: Coadministration of hesperidin with TiO 2 NPs orally for 8 weeks decreased the levels of MDA, TNF-α, AChE, and dopamine in brain homogenates, which were increased in the TiO 2 NP group. It increased the other oxidative biomarkers (SOD, CAT, and GPx) and Nrf-2 expression levels. Brain histological sections of the TiO 2 NP-treated group show degeneration, necrosis, congestion, and inflammatory cell infiltration that decreased markedly in the coadministration of hesperidin with the TiO 2 NP group. Conclusion: Hesperidin cotreatment offers significant protection against TiO 2 NP-induced oxidative stress and biochemical and histological alteration in the brain.