5109
Mai Osman Mohamed Kadry
Amelioration Of Nano sized Titanium Dioxide-Induced Oxidative Injury in Mice by Some Antioxidants
Nano sized Titanium Dioxide, nif2, smad, bax, bcl2, nkkb, il,6, tgif, tnf
This study investigates the efficacy of idebenone, carnosine and vitamin E in ameliorating some of the biochemical indices induced in the liver of titanium dioxide nanoparticles (TiO2 NPs) intoxicated mice. Nano-anatase TiO2 (21nm) was administered as a daily oral dose of 150 mg/kg for 2 weeks followed by the aforementioned antioxidants, either alone or in combination, for 1month. TiO2 NPs significantly increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Marked increments in hepatic malondialdehyde (MDA) and nitric oxide (NOx) levels along with a reduction of reduced glutathione (GSH) level, glutathione reductase (GR) and glutathione peroxidase (GPx) activities were evidenced. TiO2 NPs triggered an inflammatory response in the liver by enhancing tumor necrosis factor-α (TNF-α) and interleukin -6 (IL-6) levels. The mRNA expression of nuclear factor-erythroid-2-related factor 2 (Nrf2), nuclear factor kappa B (NF-КB) and Bax was up-regulated, whereas that of Bcl-2 was down-regulated. A significant alteration in the mRNA expression of transforming growth factor-beta (TGF-β1) and Smad-2, as well as vascular endothelium growth factor (VEGF) was also evidenced. Additionally, these NPs effectively activated caspase-3 and caused liver DNA damage. Oral administration of idebenone (200 mg/kg), carnosine (200 mg/kg) and vitamin E (100 mg/kg) alleviated the hazards of TiO2 NPs with the combination regimen showing a relatively higher effect. The histopathological and immunohistochemical examinations reinforced these results. The study highlights the anti-inflammatory and anti-apoptotic potentials of these antioxidants against TiO2 NPs- induced liver toxicity.
2016
Ph.d
Cairo
Pharmacy