title: Potential antifibrotic and angiostatic impact of idebenone, carnosine and vitamin E in nano-sized titanium dioxide-induced liver injury.
abstract: OBJECTIVE
  The present study investigated the in vitro and in vivo effects of individual and combined doses of idebenone, carnosine and vitamin E on ameliorating some of the biochemical indices of nano-sized titanium dioxide (n-TiO2) in mice liver.
  
  
  METHODS
  The in vitro cytotoxic effect of nano-sized anatase TiO2 (21 nm) on hepatic cell lines (HepG 2) was investigated. Additionally, n-TiO2 was orally administered (150 mg/kg/day) for 2 weeks, followed by a daily intragastric gavage of the aforementioned antioxidants for 1 month.
  
  
  RESULTS
  n-TiO2 induced significant cytotoxicity in hepatic cell lines and elevated the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic total antioxidant capacity (TAC) and nitrite/nitrate (NOx) levels. Meanwhile, glutathione-S-transferase (GST) activity was significantly reduced. Moreover, RT-PCR and western blot analysis showed that n-TiO2 significantly altered the mRNA and protein expressions of transforming growth factor-beta (TGF-β1) and Smad-2, as well as vascular endothelium growth factor (VEGF). Histopathological examination of hepatic tissue reinforced these results.
  
  
  CONCLUSIONS
  Idebenone, carnosine and vitamin E ameliorated the deviated parameters with the combination regimen demonstrating the most pronounced effect. Oxidative stress, liver fibrosis and angiogenesis may be implicated in n-TiO2-induced liver toxicity.
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Samy A
authors.initials: SA
authors.lastname: Abdelazim
authors.forename: Hebatallah A
authors.initials: HA
authors.lastname: Darwish
authors.forename: Sanaa A
authors.initials: SA
authors.lastname: Ali
authors.forename: Maha Z
authors.initials: MZ
authors.lastname: Rizk
authors.forename: Mai O
authors.initials: MO
authors.lastname: Kadry
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D002336:Carnosine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D014025:Titanium / Q000009:adverse effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D000975:Antioxidants; D009566:Nitrates; D009573:Nitrites; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D014451:Ubiquinone; D014810:Vitamin E; C009495:titanium dioxide; D002336:Carnosine; D014025:Titanium; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C036619:idebenone