ROLE OF POTENT ANTIOXIDANTS IN REGULATION OF SMAD-2 TRANSCRIPTION AND TGF-Î’1 SIGNALING IN NANO SIZED TITANIUM DIOXIDE-INDUCED OXIDATIVE INJURY IN MICE LIVER

Sanaa A. Ali
Therapeutic chemistry Department, National Research Center, Dokki, Gizza,Egypt.
Maha.Z.Rizk
Therapeutic chemistry Department, National Research Center, Dokki, Gizza,Egypt.
Samy A. Abdelazim
Therapeutic chemistry Department, National Research Center, Dokki, Gizza,Egypt.
Hebatallah A. Darwish
Biochemistry Department, faculty of pharmacy, Cairo University, Egypt
Mai.O.Kadry
Therapeutic chemistry Department, National Research Center, Dokki, Gizza,Egypt.

Nano-anatase TiO2 ,TGF-β1 and Smad-2 ,

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

5 , 1 , 2015