ubiquinone and titanium-dioxide

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.. 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.. 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.. 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.

Topics: Alanine Transaminase; Angiogenesis Inhibitors; Animals; Antioxidants; Aspartate Aminotransferases; Carnosine; Cell Line, Tumor; Chemical and Drug Induced Liver Injury; Glutathione Transferase; Hep G2 Cells; Humans; Liver Cirrhosis; Male; Mice; Nitrates; Nitrites; Smad2 Protein; Titanium; Transforming Growth Factor beta; Ubiquinone; Vascular Endothelial Growth Factor A; Vitamin E

The aim of this study was to investigate the toxic impacts of titanium dioxide nanoparticles (TiO₂-NPs) on rat kidneys and the possible prophylactic role of either quercetin or idebenone. TiO₂-NPs were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days to evaluate dose-dependent toxicity referred to the OECD guidelines for testing of chemicals. The results showed that administration of either low or high repeated doses of TiO₂-NPs to rats significantly increases serum kideney function biomarkers (urea, creatinine and uric acid) as well as increases in serum glucose and serum immuno- inflammatory biomarkers including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), immunoglobin g (IGg), vascular endothelial growth factor (VEGF, angiogenic factor) and nitric oxide (NO) with a concomitant decrease in renal GSH content versus normal control values. The increase in these biomarkers was more evident in rats intoxicated with high TiO₂-NPs repeated doses. Oral co- administration of either quercetin or idebenone (each 200mg/Kg body weight) daily for three weeks to rats intoxicated by either of the two doses markedly ameliorated TiO₂-NPs induced alteration in the above biomarkers. The prophylactic impacts of both agents on biochemical markers were more pronounced in rats received low TiO₂-NPs repeated doses. The biochemical investigation was supported by histological examination. In conclusion, The data showed the severity in renotoxicity of TiO₂-NPs was dose-dependent and the protective effect of quercetin and idebenone may be related to their antioxidant and anti-inflammatory properties.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Blood Glucose; Creatinine; Cytokines; Dose-Response Relationship, Drug; Inflammation Mediators; Kidney Diseases; Male; Metal Nanoparticles; Particle Size; Quercetin; Rats; Titanium; Ubiquinone; Urea

Shotgun proteomics was used to study the steady phosphorylation state of NADH:ubiquinone oxidoreductase (complex I) subunits from bovine heart mitochondria. A total tryptic digestion of enzymatically active complex I was performed, and the resulting peptide mixture was subjected to phosphopeptide enrichment by the use of titanium dioxide (TiO2). The phosphopeptide-enriched fraction was separated and analyzed with nanoscale reverse-phase HPLC-ESI-MS/MS in single information-dependent acquisition. Hence two phosphorylated complex I subunits were detected: 42 kDa and B14.5a. Phosphorylation of 42-kDa subunit at Ser-59 has already been determined with fluorescent phosphoprotein-specific gel staining and mass spectrometry (Schilling, B., Aggeler, R., Schulenberg, B., Murray, J., Row, R. H., Capaldi, R. A., and Gibson, B. W. (2005) Mass spectrometric identification of novel phosphorylation site in subunit NDUFA10 of bovine mitochondrial complex I. FEBS Lett. 579, 2485-2490). In our work, this finding was confirmed using a non-gel-based approach. In addition, we report novel phosphorylation on B14.5a nuclear encoded subunit. We demonstrated evidence of the phosphorylation site at Ser-95 residue by collision-induced dissociation experiments on three different molecular ions of two tryptic phosphopeptides of B14.5a.

Topics: Amino Acid Sequence; Animals; Binding Sites; Cattle; Electron Transport Complex I; Mitochondria; Molecular Sequence Data; Multiprotein Complexes; Myocardium; NAD; Oxidoreductases; Phosphorylation; Protein Subunits; Proteomics; Tandem Mass Spectrometry; Titanium; Ubiquinone