The expression of genes related to the Toll-like receptors (TLRs) signaling pathway were determined. Group A, B and C fed with basal diet and group D, E and F induced TD by feeding a basal diet containing 100 mg·kg-1 thiram. rGSTA3 protein was injected at 20 μg·kg-1 in group B, E and at 50 μg·kg-1 in C, F. Results suggested that lameness and death of chondrocytes were significant on day 14. TLRs signaling pathway related genes were screened based on the transcriptome enrichment, and validated on qPCR. IL-7, TLR2, 3, 4, 5, 7, 15, MyD88, MHC-II, MDA5 and TRAF6 were significantly (p < 0.05) expressed in group E and F as compared to group D on day 14 and 23. IL-7, MHCII, TRAF6, TLR3, TLR5, TLR7, and TLR15 determined insignificant in group D compared to group A on day 23. TD occur in an early phase and alleviated in the later period. rGSTA3 protein can prevent apoptosis and repair degraded chondrocytes.
- MeSH
- apoptóza MeSH
- chondrocyty fyziologie MeSH
- erytrocyty fyziologie MeSH
- glutathiontransferasa genetika metabolismus MeSH
- kur domácí imunologie MeSH
- nemoci drůbeže imunologie MeSH
- osteochondrodysplazie imunologie MeSH
- přirozená imunita MeSH
- ptačí proteiny genetika metabolismus MeSH
- rekombinantní proteiny metabolismus MeSH
- signální transdukce genetika MeSH
- thiram metabolismus MeSH
- toll-like receptory metabolismus MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Prenylflavonoids in the human organism exhibit various health-beneficial activities, although they may interfere with drugs via the modulation of the expression and/or activity of drug-metabolizing enzymes. As intestinal cells are exposed to the highest concentrations of prenylflavonoids, we decided to study the cytotoxicity and modulatory effects of the four main hop-derived prenylflavonoids on the activities and mRNA expression of the main drug-conjugating enzymes in human CaCo-2 cells. Proliferating CaCo-2 cells were used for these purposes as a model of colorectal cancer cells, and differentiated CaCo-2 cells were used as an enterocyte-like model. All the tested prenylflavonoids inhibited the CaCo-2 cells proliferation, with xanthohumol proving the most effective (IC50 8.5 μM). The prenylflavonoids modulated the activities and expressions of the studied enzymes to a greater extent in the differentiated, as opposed to the proliferating, CaCo-2 cells. In the differentiated cells, all the prenylflavonoids caused a marked increase in glutathione S-transferase and catechol-O-methyltransferase activities, while the activity of sulfotransferase was significantly inhibited. Moreover, the prenylflavonoids upregulated the mRNA expression of uridine diphosphate (UDP)-glucuronosyl transferase 1A6 and downregulated that of glutathione S-transferase 1A1/2.
- MeSH
- buněčná diferenciace účinky léků genetika MeSH
- Caco-2 buňky MeSH
- exprese genu účinky léků MeSH
- flavonoidy izolace a purifikace farmakologie MeSH
- glukuronosyltransferasa genetika metabolismus MeSH
- glutathiontransferasa genetika metabolismus MeSH
- Humulus chemie MeSH
- katechol-O-methyltransferasa genetika metabolismus MeSH
- lidé MeSH
- neopren izolace a purifikace farmakologie MeSH
- proliferace buněk účinky léků genetika MeSH
- propiofenony izolace a purifikace farmakologie MeSH
- sulfotransferasy genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
To investigate the effect of vanadyl trehalose (VT) on oxidative stress and reduced glutathione/glutathione-S-transferase (GSH/GSTs) pathway gene expression in mouse gastrointestinal tract, as well as the protective effects of vitamin C (VC) and reduced glutathione (GSH). Thirty male Kunming mice were randomly divided into five groups: control group (group A), VT group (group B), VC + VT group (group C), GSH + VT group (group D) and VC + GSH + VT group (group E). The content of reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) activity and the expressions of glutamate-cysteine ligase catalytic subunit (GCLC), glutathione synthetase (GSS), regulated through glutathione reductase (GSR) and glutathione-S-transferase pi (GSTpi) in stomach and duodenum in vanadyl trehalose treated group were lower than those in group A (P<0.05). The C, D, E group can significantly improve the above indicators, but those only in the stomach in E group reached the level of the control group. Vanadyl trehalose (VT) was able to cause oxidative stress damage to the gastrointestinal tract of mice, which affects GSH content and GSH-Px activity and interferes with the normal expression of GSH/GSTs pathway. Exogenous vitamin C, reduced glutathione and the combination of the two could play a specific role in antioxidant protection and reduce the toxicity of vanadyl trehalose.
- MeSH
- antioxidancia farmakologie MeSH
- biomimetika MeSH
- glutathion metabolismus MeSH
- glutathionperoxidasa metabolismus MeSH
- glutathionreduktasa metabolismus MeSH
- glutathiontransferasa metabolismus MeSH
- hypoglykemika farmakologie MeSH
- inzulin farmakologie MeSH
- kyselina askorbová farmakologie MeSH
- myši MeSH
- oxidační stres MeSH
- trehalosa farmakologie MeSH
- vanadáty farmakologie MeSH
- žaludek účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Climate change is expected to alter the dynamics of water masses, with consequent changes in water quality parameters such as dissolved organic carbon (DOC) concentration. DOC levels play a critical role in the fate of organic chemicals, influencing their bioavailability and toxicity to aquatic organisms. This study aimed to evaluate the effects of DOC, particularly humic acids (HA), in the toxicity of gemfibrozil (GEM) - a human pharmaceutical frequently detected in surface waters. Lethal and sublethal effects (genotoxic, biochemical and behavioural alterations) were evaluated in zebrafish embryos exposed to several concentrations of GEM and three HA levels, in a full factorial design. HA significantly increased GEM LC50 values, mainly in the first 72 h of exposure, showing a protective effect. At sublethal levels, however, such protection was not observed since HA per se elicited adverse effects. At a biochemical level, individual exposure to HA (20 mg/L) elicited significant decreases in cholinesterase and glutathione S-transferase activities. Regarding behaviour, effects of individual exposure to HA appear to surpass the GEM effects, reducing the total distance moved by larvae. Both GEM and HA significantly increased DNA damage. Hence, this study demonstrated that abiotic factors, namely HA, should be considered in the assessment of pharmaceuticals toxicity. Moreover, it showed that lethality may not be enough to characterize combined effects since different patterns of response may occur at different levels of biological organization. Testing sublethal relevant endpoints is thus recommended to achieve a robust risk assessment in realistic scenarios.
- MeSH
- chemické látky znečišťující vodu toxicita MeSH
- cholinesterasy metabolismus MeSH
- dánio pruhované embryologie fyziologie MeSH
- embryo nesavčí účinky léků MeSH
- gemfibrozil toxicita MeSH
- glutathiontransferasa metabolismus MeSH
- huminové látky škodlivé účinky MeSH
- larva účinky léků MeSH
- lékové interakce MeSH
- lidé MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Combined congenic breeding and microarray gene expression profiling previously identified glutathione S-transferase μ-type 1 (Gstm1) as a positional and functional candidate gene for blood pressure (BP) regulation in the stroke-prone spontaneously hypertensive (SHRSP) rat. Renal Gstm1 expression in SHRSP rats is significantly reduced when compared with normotensive Wistar Kyoto (WKY) rats. As Gstm1 plays an important role in the secondary defence against oxidative stress, significantly lower expression levels may be functionally relevant in the development of hypertension. The aim of this study was to investigate the role of Gstm1 in BP regulation and oxidative stress by transgenic overexpression of the Gstm1 gene. METHOD: Two independent Gstm1 transgenic SHRSP lines were generated by microinjecting SHRSP embryos with a linear construct controlled by the EF-1α promoter encoding WKY Gstm1 cDNA [SHRSP-Tg(Gstm1)1 and SHRSP-Tg(Gstm1)2]. RESULTS: Transgenic rats exhibit significantly reduced BP and pulse pressure when compared with SHRSP [systolic: SHRSP 205.2 ± 3.7 mmHg vs. SHRSP-Tg(Gstm1)1 175.5 ± 1.6 mmHg and SHRSP-Tg(Gstm1)2 172 ± 3.2 mmHg, P < 0.001; pulse pressure: SHRSP 58.4 ± 0.73 mmHg vs. SHRSP-Tg(Gstm1)1 52.7 ± 0.19 mmHg and SHRSP-Tg(Gstm1)2 40.7 ± 0.53 mmHg, P < 0.001]. Total renal and aortic Gstm1 expression in transgenic animals was significantly increased compared with SHRSP [renal relative quantification (RQ): SHRSP-Tg(Gstm1)1 1.95 vs. SHRSP 1.0, P < 0.01; aorta RQ: SHRSP-Tg(Gstm1)1 2.8 vs. SHRSP 1.0, P < 0.05]. Renal lipid peroxidation (malondialdehyde: protein) and oxidized : reduced glutathione ratio levels were significantly reduced in both transgenic lines when compared with SHRSP [malondialdehyde: SHRSP 0.04 ± 0.009 μmol/l vs. SHRSP-Tg(Gstm1)1 0.024 ± 0.002 μmol/l and SHRSP-Tg(Gstm1)2 0.021 ± 0.002 μmol/l; (oxidized : reduced glutathione ratio): SHRSP 5.19 ± 2.26 μmol/l vs. SHRSP-Tg(Gstm1)1 0.17 ± 0.11 μmol/l and SHRSP-Tg(Gstm1)2 0.47 ± 0.22 μmol/l]. Transgenic SHRSP rats containing the WKY Gstm1 gene demonstrate significantly lower BP, reduced oxidative stress and improved levels of renal Gstm1 expression. CONCLUSION: These data support the hypothesis that reduced renal Gstm1 plays a role in the development of hypertension.
- MeSH
- aorta metabolismus MeSH
- geneticky modifikovaná zvířata MeSH
- glutathion metabolismus MeSH
- glutathiontransferasa genetika metabolismus MeSH
- hypertenze genetika patofyziologie MeSH
- krevní tlak genetika MeSH
- krysa rodu rattus MeSH
- ledviny metabolismus MeSH
- malondialdehyd metabolismus MeSH
- oxidační stres genetika MeSH
- peroxidace lipidů MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- potkani transgenní MeSH
- systola MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: The palatine tonsil is a significant part of the secondary immune system. Tonsillitis and idiopathic tonsillar hypertrophy (ITH) are the most common pathologies of this component. Although there are studies on their pathogenesis, there is insufficient study of the role of antioxidant agents. Glutathione S-transferase (GST) isozymes contribute to the antioxidation reactions in the tissue via the glutathione pathway. The purpose in this study was to reveal the levels of the GST enzyme activity and protein expression of GSTP1 and GSTA1 isozymes in patients with tonsillitis and tonsil hypertrophy, and to investigate their role in the pathogenesis of these diseases. MATERIALS AND METHODS: Sixteen patients with recurrent tonsillitis and 5 patients with ITH and were included in the study. Cytosolic extracts were prepared from post-tonsillectomy tissues of both patient groups and GST enzyme activities were measured. RESULTS: The expression of GSTP1 was found to be significantly higher than GSTA1 in tissue samples of patients with ITH and recurrent tonsillitis (P<0.001). Increased GST activity and GSTP1 isozyme expression were shown in patients with recurrent tonsillitis compared to the idiopathic tonsillar hypertrophy study group. There was a positive correlation between the expressions of GSTP1 (P=0.040; r=0.47). CONCLUSION: Increased GST activity and GSTP1 isozymes were demonstrated histologically in the pathogenesis of ITH and recurrent tonsillitis. We believe that the data of changes in antioxidant capacity, obtained from studies with more extensive and larger samples, would support our findings.
- MeSH
- dítě MeSH
- glutathiontransferasa metabolismus MeSH
- hypertrofie enzymologie patofyziologie MeSH
- krční mandle enzymologie patologie MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- proteiny metabolismus MeSH
- tonzilitida enzymologie patofyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Synthetic polycyclic musks, widely used as additives in personal care products, are present in both biotic and abiotic matrices of the aquatic environment at concentrations of ng/l to µg/l. Although they are determined at comparatively low concentrations, these levels are biologically relevant and pose a significant growing risk as stressors to aquatic organisms. The purpose of our study was to evaluate the effects of 28-day-long exposure to polycyclic musk tonalide in zebrafish juvenile stages (Danio rerio) using selected biomarkers. Environmentally relevant concentrations of tonalide caused significant changes in selected enzyme activities in the experimental groups exposed to the highest concentrations. The activity of glutathione S-transferase and lipid peroxidation increased significantly (p < 0.05) after exposure to the highest concentration (50,000 ng/l) compared with the control. A similar trend was observed in catalase activity; there was a significant increase (p < 0.05) after exposure to two highest concentrations of tonalide (5000 and 50,000 ng/l). In addition, a statistically significant decrease (p < 0.05) in glutathione reductase activity was found in the lowest test concentration of tonalide (50 ng/l). None of the tested concentrations resulted in histopathological changes in liver, kidney, skin, or gill. Furthermore, no effects on body weight, body length, specific growth rate, and behavior were observed. Our results showed that tonalide exposure induced profound changes in the activities of antioxidant and detoxifying enzymes, such changes representing an adaptive response of the fish organism to tonalide toxicity.
- MeSH
- antioxidancia metabolismus MeSH
- bioindikátory účinky léků MeSH
- chemické látky znečišťující vodu toxicita MeSH
- chování zvířat účinky léků MeSH
- dánio pruhované * růst a vývoj fyziologie MeSH
- glutathiontransferasa metabolismus MeSH
- katalasa metabolismus MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- tělesná hmotnost účinky léků MeSH
- testy subchronické toxicity metody MeSH
- tetrahydronaftaleny toxicita MeSH
- žábry účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Glutathione S-transferases (GSTs) are detoxifying enzymes for a number of substrates, including some food compounds. Selected GST polymorphisms have been proven to significantly affect enzymatic activity; however, it is unclear whether this altered metabolism influences dietary composition. The objective of this study was to locate the correlation between GST polymorphisms and selected nutritional parameters, namely, fiber and vitamin C intake. METHODS: This study was conducted on a cohort of 472 individuals (mean age 45.26 years; mean body mass index [BMI] 32.36) from the South Moravian region of the Czech Republic. Basic anthropometrical parameters were measured and no association was found for the selected polymorphisms. Polymorphisms in GSTA1, GSTM1, and GSTT1 were genotyped using a polymerase chain reaction (PCR)-based methodology. Food intake was monitored using a self-administered 7-day questionnaire that was subsequently analyzed with a special focus on vitamin C intake, fiber intake, and total energy intake. RESULTS: For GSTA1 and GSTM1 polymorphisms, an association was observed with fiber intake. Though no association was found with vitamin C intake, mean vitamin C intake was found to be higher than recommended daily values. No association was found with either daily energy intake or anthropometric parameters. CONCLUSION: Based on our results, GST polymorphisms seem to affect dietary composition; however, they have no effect on total energy intake or any association with obesity.
- MeSH
- antropometrie MeSH
- dieta * MeSH
- dospělí MeSH
- energetický příjem MeSH
- genotyp MeSH
- glutathiontransferasa genetika metabolismus MeSH
- index tělesné hmotnosti MeSH
- kohortové studie MeSH
- kyselina askorbová aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita enzymologie MeSH
- polymorfismus genetický genetika MeSH
- potravní vláknina aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
In the present study, time-dependency of the induction effect of a selective inducer on the activity, protein and mRNA levels of cytochromes P450 1A1/2 (CYP1A1/2), NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTA), in primary culture of rat hepatocytes was tested and evaluated. To show the differences in responses of tested enzymes, the common aryl hydrocarbon receptor (AhR) ligand agonist, beta-naphthoflavone (BNF), was used. Induction of CYP1A1/2 by BNF was detected at all time intervals and at all levels (i.e., mRNA, protein, enzyme activity). Different responses of NQO1 and GSTA upon BNF treatment were observed. Our results demonstrate that the responses of different xenobiotic-metabolizing enzymes to the inducer vary in time and depend on the measured parameter. For these reasons, an induction study featuring only one-time interval treatment and/ or one parameter testing could produce misleading information.
- MeSH
- beta-naftoflavon metabolismus MeSH
- cytochrom P-450 CYP1A1 metabolismus MeSH
- cytochrom P-450 CYP1A2 metabolismus MeSH
- glutathiontransferasa metabolismus MeSH
- hepatocyty metabolismus MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- ligandy MeSH
- messenger RNA metabolismus MeSH
- NAD(P)H dehydrogenasa (chinon) metabolismus MeSH
- receptory aromatických uhlovodíků metabolismus MeSH
- xenobiotika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Atrazine (ATR) is a triazine herbicide banned in the European Union. It remains one of the most widely used herbicides in other parts of the world. Considering the scarcity of data on its possible harm to the environment and to human health, we assessed sub-chronic effects of a 14-day exposure at the environmentally relevant concentration of 6.86 μg/L and at 10% of the 96hLC50 (1.21 mg/L) in crayfish Cherax destructor and their recovery in a 14-day period in ATR-free water. Indicators assessed were behavior; hemolymph biochemical profile; oxidative and antioxidant parameters in gill, hepatopancreas, and muscle; and histology of gill and hepatopancreas. Crayfish exposed to the environmental concentration showed significant differences (P < 0.01) from controls in biochemical parameters of hemolymph (lactate, alkaline phosphatase) and activity of superoxide dismutase, as well as in histology of gill tissue. The higher concentration led to low motor activity, differences in biochemical profile of hemolymph (lactate, alkaline phosphatase, ammonia, glucose), antioxidant biomarkers (superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase, reduced glutathione), as well as gill and hepatopancreas histology. Some observed effects persisted after 14-days recovery in ATR-free water. The results provide evidence that environmental concentrations of ATR produce negative effects on freshwater crayfish.
- MeSH
- antioxidancia metabolismus MeSH
- atrazin toxicita MeSH
- biologické markery metabolismus MeSH
- glutathiontransferasa metabolismus MeSH
- hemolymfa účinky léků metabolismus MeSH
- hepatopankreas cytologie účinky léků MeSH
- oxidační stres účinky léků MeSH
- severní raci cytologie účinky léků metabolismus MeSH
- superoxiddismutasa metabolismus MeSH
- testy chronické toxicity * MeSH
- vystavení vlivu životního prostředí * MeSH
- žábry cytologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH