Hyperglycemia, a major metabolic disturbance present in diabetes, promotes oxidative stress. Activation of antioxidant defense is an important mechanism to prevent cell damage. Levels of heavy metals and their binding proteins can contribute to oxidative stress. Antiradical capacity and levels of metallothionein (MT), metals (zinc and copper), and selected antioxidants (bilirubin, cysteine, and glutathione) were determined in 70 type 2 diabetes mellitus (T2DM) subjects and 80 healthy subjects of Caucasian origin. Single nucleotide polymorphism (rs28366003) in MT gene was detected. Antiradical capacity, conjugated bilirubin, and copper were significantly increased in diabetics, whereas MT and glutathione were decreased. Genotype AA of rs28366003 was associated with higher zinc levels in the diabetic group. The studied parameters were not influenced by renal function. This is the first study comprehensively investigating differences in MT and metals relevant to oxidative stress in T2DM. Ascertained differences indicate increased oxidative stress in T2DM accompanied by abnormalities in non-enzymatic antioxidant defense systems.
- MeSH
- biologické markery krev MeSH
- chronická renální insuficience krev genetika patofyziologie MeSH
- diabetes mellitus 2. typu komplikace MeSH
- diabetické nefropatie krev genetika patofyziologie MeSH
- genetické asociační studie MeSH
- jednonukleotidový polymorfismus MeSH
- ledviny patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- měď krev MeSH
- metalothionein krev genetika MeSH
- oxidační stres * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci MeSH
- zinek krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
In this study, the effects of tributyltin (TBT) on biochemical parameters (antioxidant responses and Na(+) -K(+) -ATPase) in different tissues were investigated by using juvenile common carp (Cyprinus Carpio) as well as growth and ion regulation-related genes expression and stress-related proteins profiling in fish liver. Oxidative stress indices and Na(+) -K(+) -ATPase showed tissues-specific responses in fish exposed to different TBT concentrations. All tested genes related to GH/IGF-I axis and ion-regulation were significantly induced in the TBT group with lower concentrations (except for the igfbp3 in 10 μg/L) and were inhibited in 20 μg/L. In addition, the profiling of two proteins Hsp 70 and MT were increasing in a dose-dependent manner under TBT stress. In short, TBT-induced biochemical and molecular responses in different tissues were reflected in the measured parameters in the test. On the basis of TBT residue levels in the natural environment, more long-term experiments at lower concentrations will be necessary in the future.
- MeSH
- antioxidancia metabolismus MeSH
- chemické látky znečišťující vodu toxicita MeSH
- insulinu podobný růstový faktor I biosyntéza MeSH
- játra účinky léků metabolismus MeSH
- kapři růst a vývoj MeSH
- oxidační stres účinky léků MeSH
- proteiny tepelného šoku biosyntéza MeSH
- regulace genové exprese účinky léků MeSH
- růstový hormon biosyntéza MeSH
- sodíko-draslíková ATPasa biosyntéza MeSH
- trialkylcínové sloučeniny toxicita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Sibutramine is a serotonin-norepinephrine reuptake inhibitor that was used for weight-loss management in obese patients. Even though it was officially withdrawn from the market in 2010, it is still present in some tainted weight-loss pills (as reported by US Food and Drug Administration). Thus, it is still reasonable to study the effects of this compound. The aim of this work was to investigate the potential of sibutramine to induce CYP1A1/CY3A4 in human cancer cell lines and CYP1A1/2, CYP2A6, CYP2B6, and CYP3A4 in human hepatocytes, a competent model of metabolically active cells. The levels of mRNA and protein of CYP1A1/1A2/3A4/2A6/2B6 were compared with the typical inducers, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and rifampicin (RIF) for CYP1A1/2 and for other CYPs, respectively. The mRNA and protein levels of all genes in either cancer cell lines or human hepatocytes were induced when treated with typical inducers but not with sibutramine.
- MeSH
- cyklobutany farmakologie MeSH
- hepatocyty účinky léků enzymologie MeSH
- izoenzymy biosyntéza MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- látky proti obezitě farmakologie MeSH
- lidé MeSH
- messenger RNA genetika izolace a purifikace MeSH
- nádorové buněčné linie MeSH
- primární buněčná kultura MeSH
- systém (enzymů) cytochromů P-450 biosyntéza MeSH
- western blotting MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- aromatické hydroxylasy metabolismus MeSH
- cytochrom P-450 CYP1A2 metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- glykosidy farmakologie chemie MeSH
- hepatocyty enzymologie účinky léků MeSH
- lidé MeSH
- N-demethylasy metabolismus MeSH
- regulace genové exprese enzymů účinky léků MeSH
- silymarin farmakologie chemie MeSH
- Check Tag
- lidé MeSH
