ROLE OF POTENT ANTIOXIDANTS IN REGULATION OF SMAD-2 TRANSCRIPTION AND TGF-Β1 SIGNALING IN NANO SIZED TITANIUM DIOXIDE-INDUCED OXIDATIVE INJURY IN MICE LIVER

The present study investigated the efficacy of individual and combined doses of Idebenone, carnosine and vitamin E in ameliorating some biochemical indices of nano sized Titanium dioxide (n-TiO2) in mice liver. Nano-anatase TiO2 (21 nm)was administered as a daily oral dose of 150 mg/Kg for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. N-TiO2 induced a significant up regulation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarker [nitrite/nitrate level] (NOx). While it significantly down regulated glutathione reductase (GR) and glutathione peroxidase (GPx) activities. More over the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors transforming growth factor-beta (TGF-β1) and Smad-2 and angiogenesis factor vascular endothelium growth factor (VEGF). Histopathological examination of hepatic tissue reinforced the previous biochemical results. idebenone, carnosine and vitamin E ameliorated the deviated parameters with a variable degree with the most pronounced role in alleviating the hazardous effect of n-TiO2 toxicity following the combination regimen. Our results also implied that the oxidative stress and liver injury may be involved in nano-anatase TiO2-induced liver toxicity