This research demonstrated the protective effect and possible mechanism of the Sophora viciifolia extract (SVE) against acetaminophen-induced liver injury in mice. The levels of ALT and AST in the serum and antioxidant enzyme activity in the liver were measured. We used immunohistochemistry to detect CYP2E1, Nrf2, and Keap1 protein expression in the liver. The mRNA expression in the liver of TNF-α, NF-κB, and IL-6, Nrf2 and its downstream genes HO-1 and GCLC were measured by qRT-PCR. We found that SVE could decrease the ALT and AST levels, promote the activities of SOD, CAT, GSH-Px, and GSH, and ameliorate pathological liver lesions. SVE could down-regulate the mRNA expression of inflammatory factors and up-regulate Nrf2, HO-1 and GCLC. SVE reduced the protein expression of the CYP2E1 and increased the Nrf2 and Keap1. SVE has been shown to have a protective effect against APAP-induced liver injury, possibly through activation of the Keap1-Nrf2 pathway.

• MeSH
• antioxidancia farmakologie   MeSH
• chronické poškození jater způsobené chemickými látkami * MeSH
• cytochrom P-450 CYP2E1 genetika   metabolismus   MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• KEAP-1 genetika   metabolismus   MeSH
• messenger RNA MeSH
• myši MeSH
• ovoce metabolismus   MeSH
• paracetamol * škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Dihydromyricetin (DHM) is a natural flavonoid showing several health promoting effects such as protective activity during severe alcohol intoxication. The mechanism underlying the effects of DHM on alcohol metabolism is virtually unknown. The present paper is focused on clarifying the role of DHM in the liver alcohol elimination at its molecular level. First, impact of DHM on alcohol dehydrogenase (ADH) activity in vitro and the enzyme induction in vivo was examined. Neither the ADH activity nor the enzyme expression were influenced by DHM. Next, the effect of DHM during alcohol intoxication were studied on primary hepatocytes isolated from EtOH-premedicated and untreated rats. The viability of cells exposed to alcohol, estimated based on the released enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), was slightly affected by DHM. Although the expected hepatoprotective effect of DHM was not fully achieved, DHM (in a concentration manner) proved to reduce the level of ROS/RNS in hepatocytes. However, no change in the rate of alcohol metabolism in vivo was found when rats were administered with a single or repeated dose of ethanol supplemented with DHM. In conclusion, the proposed positive effect of DHM during alcohol intoxication has not been proven. Moreover, there is no effect of DHM on the alcohol metabolism. The "hoped-for" DHM hepatoprotective activity can be attributed to the reduction of ROS/RNS levels in cells.

• MeSH
• alkoholdehydrogenasa metabolismus   MeSH
• antioxidancia farmakologie   MeSH
• cytochrom P-450 CYP2E1 metabolismus   MeSH
• ethanol metabolismus   MeSH
• flavonoly farmakologie   MeSH
• hepatocyty účinky léků   metabolismus   MeSH
• játra účinky léků   metabolismus   MeSH
• kultivované buňky MeSH
• metabolická inaktivace MeSH
• nitrosativní stres účinky léků   MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• reaktivní formy dusíku metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The hepatic cytochrome p450 enzymes 1 A, 2A19 and 2E1 is very important for the elimination of skatole from the body of pigs. Impaired skatole metabolism, results in skatole accumulation, which give rise to off flavor of the meat. Several metabolites of skatole has been identified, however the role of these metabolites in the inhibition of the skatole metabolizing enzymes are not documented. Using microsomes from pigs and fish, we determined the ability of several skatole metabolites to inhibit CYP1 A, CYP2A19 and CYP2E1 dependent activity. Our results show that 2-aminoacetophenone is an inhibitor of porcine CYP2A19 and CYP2E1 activity, but not the piscine orthologues. In conclusion, there is species specific differences in the inhibition of CYP1 A and CYP2A19 dependent metabolism of probe substrates. This is relevant to the evaluation of different model systems and to the reduction of off flavor of meat.

• MeSH
• acetofenony toxicita   MeSH
• červené maso analýza   MeSH
• cytochrom P-450 CYP1A1 antagonisté a inhibitory   metabolismus   MeSH
• cytochrom P-450 CYP2E1 metabolismus   MeSH
• druhová specificita MeSH
• inhibitory cytochromu P450 CYP2E1 toxicita   MeSH
• jaterní mikrozomy účinky léků   metabolismus   MeSH
• játra účinky léků   metabolismus   MeSH
• kumariny toxicita   MeSH
• nitrofenoly toxicita   MeSH
• oxaziny toxicita   MeSH
• potrava z moře (živočišná) analýza   MeSH
• prasata MeSH
• ryby MeSH
• skatol toxicita   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Cytochrome P450 (CYP) is a major group of enzymes, which conduct Phase I metabolism. Among commonly used animal models, the pig has been suggested as the most suitable model for investigating drug metabolism in human beings. Moreover, porcine CYP2A19 and CYP2E1 are responsible for the biotransformation of both endogenous and exogenous compounds such as 3-methylindole (skatole), sex hormones and food compounds. However, little is known about the regulation of porcine CYP2A19 and CYP2E1. In this MiniReview, we summarise the current knowledge about the regulation of porcine CYP2A19 and CYP2E1 by environmental, biological and dietary factors. Finally, we reflect on the need for further research, to clarify the interaction between active feed components and the porcine CYP system.

• MeSH
• biotransformace MeSH
• cytochrom P-450 CYP2E1 genetika   metabolismus   MeSH
• cytochrom P450 CYP2A6 genetika   metabolismus   MeSH
• krmivo pro zvířata * MeSH
• lidé MeSH
• pohlavní steroidní hormony metabolismus   MeSH
• prasata metabolismus   MeSH
• sekvenční homologie MeSH
• skatol metabolismus   MeSH
• xenobiotika metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• Klíčová slova
• HHTg potkani,
• MeSH
• cytochrom P-450 CYP2E1 účinky léků   MeSH
• fenofibrát * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• hydroxymethylglutaryl-CoA-reduktasy účinky léků   MeSH
• metabolický syndrom * farmakoterapie   MeSH
• P-glykoprotein účinky léků   MeSH
• potkani Wistar MeSH
• silymarin * aplikace a dávkování   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• cirkadiánní hodiny MeSH
• cirkadiánní rytmus * MeSH
• cytochrom P-450 CYP2E1 MeSH
• exprese genu MeSH
• genetická transkripce MeSH
• hepatocyty MeSH
• léková chronoterapie MeSH
• lékové interakce MeSH
• lidé MeSH
• paracetamol škodlivé účinky   MeSH
• péče orientovaná na pacienta MeSH
• proteiny CLOCK MeSH
• transkripční faktory ARNTL MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Within fossil- and solid-fuel dependent geographic locations, mechanisms of air pollution-induced asthma remains unknown. In particular, sources of greater genetic susceptibility to airborne carcinogen, namely, benzo[a]pyrene (B[a]P) has never been investigated beyond that of a few well known genes. OBJECTIVES: To deepen our understanding on how the genotypic variations within the candidate genes contribute to the variability in the children's susceptibility to ambient B[a]P on doctor-diagnosed asthma. METHODS: Clinically confirmed asthmatic versus healthy control children (aged, 7-15) were enrolled from historically polluted and rural background regions in Czech Republic. Contemporaneous ambient B[a]P concentration was obtained from the routine monitoring network. The sputum DNA was genotyped for 95 genes. B[a]P interaction with SNPs was studied by two-stage, semi-agnostic screening of 621 SNPs. RESULTS: The median B[a]P within the highly polluted urban center was 8-times higher than that in the background region (7.8 vs. 1.1 ng/m3) during the period of investigation. Within the baseline model, which considered B[a]P exposure-only, the second tertile range was associated with a significantly reduced odds (aOR = 0.28) of asthma (95% CI, 0.16 to 0.50) compared to those at the lowest range. However, the highest range of B[a]P was associated with 3.18-times greater odds of the outcome (95% CI, 1.77 to 5.71). Within the gene-environment interaction models, joint occurrence of a high B[a]P exposure range and having a high-risk genotype at CTLA4 gene (rs11571316) was associated with 9-times greater odds (95% CI, 4.56-18.36) of the asthma diagnosis. Similarly, rs11571319 at CTLA4 and a high B[a]P exposure range was associated with a 8-times greater odds (95% CI, 3.95-14.27) of asthma diagnosis. Furthermore, having TG + GG genotypes on rs1031509 near STAT4 was associated with 5-times (95% CI, 3.03-8.55) greater odds of asthma diagnosis at the highest B[a]P range, compared to the odds at the reference range. Also CYP2E1 AT + TT genotypes (rs2070673) was associated with 5-times (95% CI, 3.1-8.8) greater odds of asthma diagnosis at the highest B[a]P exposure. CONCLUSIONS: The children, who jointly experience a high B[a]P exposure (6.3-8.5 ng/m3) as well as susceptible genotypes in CTLA4 (rs11571316 and rs11571319), STAT4 (rs1031509), and CYP2E1 (rs2070673), respectively, are associated with a significantly greater odds of having doctor-diagnosed asthma, compared to those with neither risk factors.

• MeSH
• antigen CTLA-4 genetika   MeSH
• benzopyren analýza   MeSH
• bronchiální astma chemicky indukované   genetika   MeSH
• cytochrom P-450 CYP2E1 genetika   MeSH
• dítě MeSH
• genetická predispozice k nemoci * MeSH
• genotyp MeSH
• interakce genů a prostředí MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• městské obyvatelstvo MeSH
• studie případů a kontrol MeSH
• transkripční faktor STAT4 genetika   MeSH
• venkovské obyvatelstvo MeSH
• vystavení vlivu životního prostředí analýza   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• znečištění ovzduší analýza   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

The occurrence of boar taint in meat from uncastrated males may significantly affect the economics of pork production. The aim of this study was to analyse associations of four single nucleotide polymorphisms (SNPs) in the porcine CYP2E1 gene with skatole, indole, and androstenone levels in the Czech Large White-Czech Landrace commercial crossbreds. The SNPs were: g.2412C>T, c.1422C>T, c.1423G>A and c.*14G>T. Skatole, indole and androstenone levels were estimated by HPLC, and genotypes at the SNPs were determined by PCR-RFLP. SNPs c.1423G>A and c.*14G>T were in complete linkage disequilibrium. In boars, all SNPs were associated with the indole levels (P<0.05; P<0.01). There also were differences in the skatole levels in different genotypes, but these were not significant. No associations with androstenone levels were found. The associations of the SNPs with indole compounds should be studied in other commercial populations of boars to verify the favourable alleles and genotypes, with the prospect for their application in marker-assisted selection.

• MeSH
• androsteny analýza   MeSH
• červené maso MeSH
• cytochrom P-450 CYP2E1 genetika   MeSH
• genetické asociační studie MeSH
• indoly analýza   MeSH
• jednonukleotidový polymorfismus * MeSH
• křížení genetické MeSH
• mapování chromozomů MeSH
• skatol analýza   MeSH
• Sus scrofa genetika   MeSH
• tuková tkáň chemie   MeSH
• vazebná nerovnováha MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

This is the first in vitro study to investigate gender-related differences in the regulation of human cytochrome P450 by the flavonoids. Activities of CYP2E1 and CYP3A were measured in the presence of quercetin, myricetin, or isorhamnetin in hepatic microsomal pools from male and female donors. Hydroxylation of p-nitrophenol (PNPH) was measured to determine CYP2E1 activity, and O-dealkylation of 7-benzyloxy-4-trifluoromethylcoumarin (BFC) was measured to determine CYP3A activity. Quercetin, but not myricetin or isorhamnetin, competitively inhibited PNPH activity in human recombinant cDNA-expressed CYP2E1 with the Ki=52.1±6.31μM. In the human microsomes, slight inhibition of PNPH activity by quercetin was not considered as physiologically relevant. Quercetin inhibited BFC activity in human recombinant cDNA-expressed CYP3A4 competitively with the Ki=15.4±1.52μM, and myricetin - noncompetitively with the Ki=74.6±7.99μM. The degree of inhibition by quercetin was similar between genders. Myricetin showed somewhat stronger inhibition in female pools, but the Ki values were higher than physiologically relevant concentrations. Isorhamnetin did not affect either PNPH or BFC activity. We concluded that observed inhibition of CYP2E1 and CYP3A by some flavonols were not gender-dependent.

• MeSH
• cytochrom P-450 CYP2E1 metabolismus   MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• flavonoidy farmakologie   MeSH
• hydroxylace MeSH
• inhibitory cytochromu P450 CYP2E1 farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• jaterní mikrozomy účinky léků   metabolismus   MeSH
• kumariny metabolismus   MeSH
• lidé MeSH
• nitrofenoly metabolismus   MeSH
• quercetin analogy a deriváty   farmakologie   MeSH
• sexuální faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Consumption of dietary supplements with green tea extract (GTE) is popular for weight management, but it may be accompanied by various side effects, including interactions with drugs. The aim of the present in vivo study was to evaluate the effect of defined GTE (Polyphenon 60) in three dosage schemes on insulin, leptin and drug-metabolizing enzymes in obese mice. METHODS: Experimental obesity was induced by repeated s.c. application of monosodium glutamate to newborn mice. Green tea extract was administered in three dosage schemes in chow diet. The plasmatic levels of insulin and leptin were assayed using enzyme-linked immunosorbent assay. Enzyme activities and mRNA expressions of drug-metabolizing enzymes (totally 13) were analyzed in liver and small intestine using spectrophotometric and HPLC assays and RT-PCR, respectively. RESULTS: GTE-treatment decreased insulin and leptin levels. Eleven enzymes were significantly affected by GTE-treatment. Long-term administration of 0.01% GTE caused increase in the activity and mRNA level of cytochrome P450 3A4 (CYP3A4) ortholog in the liver as well as in the small intestine. Interestingly, short-term overdose by GTE (0.1%) had more pronounced effects on enzyme activities and mRNA expressions than long-term overdose. CONCLUSIONS: GTE-mediated induction of CYP3A4 ortholog, the main drug-metabolizing enzyme, could result in decreased efficacy of simultaneously or subsequently administered drug in obese individuals.

• MeSH
• antioxidancia farmakologie   MeSH
• aromatické hydroxylasy genetika   metabolismus   MeSH
• čaj chemie   MeSH
• cytochrom P-450 CYP2E1 genetika   metabolismus   MeSH
• cytochrom P-450 CYP3A genetika   metabolismus   MeSH
• ELISA MeSH
• glutamát sodný škodlivé účinky   MeSH
• inzulin krev   MeSH
• játra účinky léků   metabolismus   MeSH
• leptin krev   MeSH
• messenger RNA genetika   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši obézní MeSH
• myši MeSH
• obezita chemicky indukované   farmakoterapie   MeSH
• potravní doplňky * MeSH
• rostlinné extrakty farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH