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[PMID]:26913515
[Au] Autor:Ma J; Wang J; Cheng J; Xiao W; Fan K; Gu J; Yu B; Yin G; Wu J; Ren J; Hou J; Jiang Y; Tan Y; Jin W
[Ad] Endereço:Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, People's Republic of China.
[Ti] Título:Impacts of Blast-Induced Traumatic Brain Injury on Expressions of Hepatic Cytochrome P450 1A2, 2B1, 2D1, and 3A2 in Rats.
[So] Source:Cell Mol Neurobiol;37(1):111-120, 2017 Jan.
[Is] ISSN:1573-6830
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The hepatic cytochrome P450 (CYP450) enzyme superfamily is one of the most important drug-metabolizing enzyme systems, which is responsible for the metabolism of a large number of clinically relevant medications used in traumatic brain injury (TBI) therapy. Modification of CYP450 expression may have important influences on drug metabolism and lead to untoward effects on those with narrow therapeutic windows. However, the impact of blast-induced TBI (bTBI) on the expression of CYP450 has received little attention. The subfamilies of CYP1A, 2B, 2D, and 3A account for about 85 % of all human drug metabolism of clinical significance. Therefore, in this study, we investigated the expressions of hepatic CYP1A2, CYP2B1, CYP2D1, and CYP3A2 in rats suffering bTBI. Meanwhile, we also measured some important cytokines in serum after injury, and calculated the correlation between these cytokines and the expressions of CYP1A2, CYP2B1, CYP2D1, and CYP3A2. The results showed that bTBI could significantly reduce mRNA expressions of CYP1A2, CYP2D1, and CYP3A2 at the early stage and induce the expressions from 48 h to 1 week after injury. The protein expressions of these CYP450s had all been downregulated from 24 to 48 h post- injury, and then began to elevate at 48 h after bTBI. The cytokines, IL-1ß, IL-2, IL-6, and TNF-α, increased significantly in the early phase, and began to reduce at the delayed phase of bTBI. The serum levels of IL-1ß, IL-6, and TNF-α but not IL-2 were significantly negative correlated with the mRNA expressions of CYP2B1 and CYP2D1 and the proteins expressions of CYP1A2, CYP2B1, CYP2D1, and CYP3A2. In conclusion, our work has, for the first time, indicated that bTBI has significant impact on the expressions of CYP1A2, CYP2B1, CYP2D1, and CYP3A2, which may be related to the cytokines induced by the injury.
[Mh] Termos MeSH primário: Lesões Encefálicas Traumáticas/enzimologia
Citocromo P-450 CYP1A2/biossíntese
Citocromo P-450 CYP2B1/biossíntese
Citocromo P-450 CYP3A/biossíntese
Família 2 do Citocromo P450/biossíntese
Fígado/enzimologia
[Mh] Termos MeSH secundário: Animais
Lesões Encefálicas Traumáticas/patologia
Citocromo P-450 CYP1A2/genética
Citocromo P-450 CYP2B1/genética
Citocromo P-450 CYP3A/genética
Família 2 do Citocromo P450/genética
Regulação Enzimológica da Expressão Gênica
Masculino
Microssomos Hepáticos/enzimologia
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.14.14.1 (Cyp1a2 protein, rat); EC 1.14.14.1 (Cyp2d1 protein, rat); EC 1.14.14.1 (Cyp3a2 protein, rat); EC 1.14.14.1 (Cytochrome P-450 CYP1A2); EC 1.14.14.1 (Cytochrome P-450 CYP2B1); EC 1.14.14.1 (Cytochrome P-450 CYP3A); EC 1.14.14.1 (Cytochrome P450 Family 2)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160226
[St] Status:MEDLINE
[do] DOI:10.1007/s10571-016-0351-6


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[PMID]:27828666
[Au] Autor:Da Costa NM; Visoni SB; Dos Santos IL; Barja-Fidalgo TC; Ribeiro-Pinto LF
[Ad] Endereço:Laboratório de Toxicologia e Biologia Molecular, Departamento de Bioquímica, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
[Ti] Título:Maternal protein restriction during lactation modulated the expression and activity of rat offspring hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2, and CYP2E1 during development.
[So] Source:Braz J Med Biol Res;49(11):e5238, 2016.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring's CYPs during 90 days after birth, using Wistar rats as a mammal model. Hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2 and CYP2E1 mRNA and protein expression, and associated catalytic activities (ECOD, EROD, MROD, BROD, PROD and PNPH) were evaluated in 15-, 30-, 60-, and 90-day-old offspring from dams fed with either a 0% protein (MPR groups) or a standard diet (C groups) during the 10 first days of lactation. Results showed that most CYP genes were induced in 60- and 90-day-old MPR offspring. The inductions detected in MPR60 and MPR90 were of 5.0- and 2.0-fold (CYP1A2), 3.7- and 2.0-fold (CYP2B2) and 9.8- and 5.8- fold (CYP2E1), respectively, and a 3.8-fold increase of CYP2B1 in MPR90. No major alterations were detected in CYP protein expression. The most relevant CYP catalytic activities' alterations were observed in EROD, BROD and PNPH. Nevertheless, they did not follow the same pattern observed for mRNA expression, except for an induction of EROD in MPR90 (3.5-fold) and of PNPH in MPR60 (2.2-fold). Together, these results suggest that MPR during lactation was capable of altering the expression and activity of the hepatic CYP enzymes evaluated in the offspring along development.
[Mh] Termos MeSH primário: Sistema Enzimático do Citocromo P-450/metabolismo
Dieta com Restrição de Proteínas
Lactação/metabolismo
Fígado/enzimologia
[Mh] Termos MeSH secundário: Animais
Hidrocarboneto de Aril Hidroxilases/metabolismo
Citocromo P-450 CYP1A1/metabolismo
Citocromo P-450 CYP1A2/metabolismo
Citocromo P-450 CYP2B1/metabolismo
Citocromo P-450 CYP2E1/metabolismo
Feminino
Modelos Animais
Ratos
Ratos Wistar
Esteroide Hidroxilases/metabolismo
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.14.- (Steroid Hydroxylases); EC 1.14.13.- (Cytochrome P-450 CYP2E1); EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases); EC 1.14.14.1 (Cytochrome P-450 CYP1A1); EC 1.14.14.1 (Cytochrome P-450 CYP1A2); EC 1.14.14.1 (Cytochrome P-450 CYP2B1); EC 1.14.14.1 (steroid 16-beta-hydroxylase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161110
[St] Status:MEDLINE


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[PMID]:27594096
[Au] Autor:Mahiout S; Pohjanvirta R
[Ad] Endereço:Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Mustialankatu 1, FI-00790 Helsinki, Finland. Electronic address: selma.mahiout@helsinki.fi.
[Ti] Título:Aryl hydrocarbon receptor agonists trigger avoidance of novel food in rats.
[So] Source:Physiol Behav;167:49-59, 2016 Dec 01.
[Is] ISSN:1873-507X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of dioxins, but also plays important physiological roles, which are only beginning to unfold. Previous studies have surprisingly unveiled that low doses of the potent AHR agonist TCDD induce a strong and persistent avoidance of novel food items in rats. Here, we further examined the involvement of the AHR in the avoidance response in Sprague-Dawley rats with three established AHR agonists: 6-formylindolo(3,2-b)carbazole (FICZ), ß-naphthoflavone (BNF) and benzo[a]pyrene (BaP); with a novel selective AHR modulator (C2); and with an activator of another nuclear receptor, CAR: 2,4,6-tryphenyldioxane-1,3 (TPD). As sensitive indices of AHR or CAR activity, we used Cyp1a1 and Cyp2b1 gene expression, as they are, respectively, the drug-metabolizing enzymes specifically regulated by them. We further attempted to address the roles played by enhanced neophobia and conditioned taste aversion (CTA) in the avoidance behaviour. All AHR agonists triggered practically total avoidance of novel chocolate, but the durations varied. Likewise, acutely subtoxic doses of C2, differing by 25-fold, all elicited a similar outcome. In contrast, TPD did not influence chocolate consumption at all. If rats were initially accustomed to chocolate for 6h after single FICZ or BNF exposure, avoidance was still clearly present two weeks later when chocolate was offered again. Hence, the avoidance response appears to specifically involve the AHR instead of being triggered by induction of intestinal or hepatic nuclear receptor signalling in general. It is also shared by both endogenous and exogenous AHR activators. Moreover, this behavioural change in rats seems to contain elements of both CTA and enhanced neophobia, but further clarification of this is still required.
[Mh] Termos MeSH primário: Aprendizagem da Esquiva/efeitos dos fármacos
Comportamento Alimentar/efeitos dos fármacos
Preferências Alimentares/efeitos dos fármacos
Receptores de Hidrocarboneto Arílico/agonistas
Paladar/efeitos dos fármacos
[Mh] Termos MeSH secundário: Análise de Variância
Animais
Benzo(a)pireno/metabolismo
Benzo(a)pireno/farmacologia
Carbazóis/farmacologia
Citocromo P-450 CYP1A1/genética
Citocromo P-450 CYP1A1/metabolismo
Citocromo P-450 CYP2B1/genética
Citocromo P-450 CYP2B1/metabolismo
Relação Dose-Resposta a Droga
Ingestão de Alimentos/efeitos dos fármacos
Masculino
RNA Mensageiro/metabolismo
Ratos
Ratos Sprague-Dawley
Receptores de Hidrocarboneto Arílico/metabolismo
Fatores de Tempo
beta-Naftoflavona/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (6-formylindolo(3,2-b)carbazole); 0 (Carbazoles); 0 (RNA, Messenger); 0 (Receptors, Aryl Hydrocarbon); 3417WMA06D (Benzo(a)pyrene); 6051-87-2 (beta-Naphthoflavone); EC 1.14.14.1 (Cytochrome P-450 CYP1A1); EC 1.14.14.1 (Cytochrome P-450 CYP2B1)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170623
[Lr] Data última revisão:
170623
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160906
[St] Status:MEDLINE


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[PMID]:27455552
[Au] Autor:Nagai K; Fukuno S; Suzuki H; Konishi H
[Ti] Título:Higher gene expression of CYP1A2, 2B1 and 2D2 in the brain of female compared with male rats.
[So] Source:Pharmazie;71(6):334-6, 2016 Jun.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Cytochrome P450 (CYP) in the brain plays an essential role in the local metabolism of various compounds, including clinically used drugs, toxins, and endogenous substances. In the present study, we compared the expression profiles of mRNAs for several CYP subtypes in the brain between male and female rats. The expression of CYP1A2, CYP2B1, and CYP2D2 in females was significantly higher than that in males. On the other hand, the expression level of the other CYP subtypes examined in the male brain was similar to that in the female brain. These results strongly suggest that marked gender differences exist in the expression profiles of some CYP subtypes in rat brain.
[Mh] Termos MeSH primário: Hidrocarboneto de Aril Hidroxilases/genética
Química Encefálica/genética
Citocromo P-450 CYP2B1/genética
Citocromos/genética
[Mh] Termos MeSH secundário: Animais
Hidrocarboneto de Aril Hidroxilases/biossíntese
Citocromo P-450 CYP1A2
Citocromo P-450 CYP2B1/biossíntese
Citocromos/biossíntese
Feminino
Regulação Enzimológica da Expressão Gênica
Masculino
Reação em Cadeia da Polimerase
Ratos
Ratos Wistar
Caracteres Sexuais
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytochromes); EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases); EC 1.14.14.1 (Cyp1a2 protein, rat); EC 1.14.14.1 (Cyp2d2 protein, rat); EC 1.14.14.1 (Cytochrome P-450 CYP1A2); EC 1.14.14.1 (Cytochrome P-450 CYP2B1)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160727
[St] Status:MEDLINE


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[PMID]:27387539
[Au] Autor:McPhail BT; White CA; Cummings BS; Muralidhara S; Wilson JT; Bruckner JV
[Ad] Endereço:Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy and Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA.
[Ti] Título:The immature rat as a potential model for chemical risks to children: Ontogeny of selected hepatic P450s.
[So] Source:Chem Biol Interact;256:167-77, 2016 Aug 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Concern about potential susceptibilities of infants and children to chemicals has led to the consideration of immature rodents as potential test surrogates. Maturation of some hepatic microsomal cytochrome P450s (CYPs), that participate in metabolic activation of organic solvents and polycyclic aromatic hydrocarbons (PAHs), may differ significantly between humans and rodents. The present investigation was undertaken to delineate the ontogeny of selected hepatic CYPs in male and female Sprague-Dawley (S-D) rats, and to contrast them with developmental profiles in humans. Microsomes were prepared from the liver of sexed and unsexed postnatal day (PND) 1-90 rats, and total CYP450 levels, as well as CYP1A1/2, CYP2E1 and CYP2B1/2 activities and protein, were quantified. CYP1A1/2 and CYP2E1 activity and expression rose rapidly after birth, peaked from PND 21-40/50, and declined substantially to adult values by PND 90. The same ontogenic profiles were manifested when the enzyme activities were expressed per entire liver or liver normalized to body weight. CYP1A1/2 and CYP2E1 activity and protein expression were well correlated. CYP2B1/2 activity peaked abruptly on PND 21 and declined irregularly to adult values. These patterns are in contrast to human CYP1A2 and CYP2E1, which are reported to progressively increase in liver during the first few months to years of life. The three CYP protein developmental profiles were largely gender independent in rats. The immature rat does not appear to be a suitable model for assessing risks posed to infants and children by chemicals metabolically activated by CYP2E1, based on the findings of greater carbon tetrachloride hepatotoxicity in preweanlings and weanlings than in adult animals. Additional studies are required to determine whether immature S-D rats may be used as an animal model for substrates of other CYPs, as total CYP450 levels in the liver progressively rose during maturation, similarly to humans.
[Mh] Termos MeSH primário: Tetracloreto de Carbono/toxicidade
Doença Hepática Induzida por Substâncias e Drogas/etiologia
Sistema Enzimático do Citocromo P-450/metabolismo
Fígado/efeitos dos fármacos
Fígado/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Ativação Metabólica/efeitos dos fármacos
Fatores Etários
Animais
Hidrocarboneto de Aril Hidroxilases/metabolismo
Doença Hepática Induzida por Substâncias e Drogas/metabolismo
Doença Hepática Induzida por Substâncias e Drogas/patologia
Criança
Citocromo P-450 CYP1A1/metabolismo
Citocromo P-450 CYP1A2/metabolismo
Citocromo P-450 CYP2B1/metabolismo
Citocromo P-450 CYP2E1/metabolismo
Feminino
Seres Humanos
Fígado/metabolismo
Fígado/patologia
Masculino
Microssomos Hepáticos/efeitos dos fármacos
Microssomos Hepáticos/metabolismo
Ratos
Ratos Sprague-Dawley
Medição de Risco
Esteroide Hidroxilases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9035-51-2 (Cytochrome P-450 Enzyme System); CL2T97X0V0 (Carbon Tetrachloride); EC 1.14.- (Steroid Hydroxylases); EC 1.14.13.- (Cytochrome P-450 CYP2E1); EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases); EC 1.14.14.1 (Cytochrome P-450 CYP1A1); EC 1.14.14.1 (Cytochrome P-450 CYP1A2); EC 1.14.14.1 (Cytochrome P-450 CYP2B1); EC 1.14.14.1 (steroid 16-beta-hydroxylase)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170130
[Lr] Data última revisão:
170130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE


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[PMID]:27321734
[Au] Autor:Cho SJ; Kim SB; Cho HJ; Chong S; Chung SJ; Kang IM; Lee JI; Yoon IS; Kim DD
[Ad] Endereço:College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , Seoul 08826, Republic of Korea.
[Ti] Título:Effects of Nonalcoholic Fatty Liver Disease on Hepatic CYP2B1 and in Vivo Bupropion Disposition in Rats Fed a High-Fat or Methionine/Choline-Deficient Diet.
[So] Source:J Agric Food Chem;64(27):5598-606, 2016 Jul 13.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nonalcoholic fatty liver disease (NAFLD) refers to hepatic pathologies, including simple fatty liver (SFL), nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis, that may progress to hepatocellular carcinoma. These liver disease states may affect the activity and expression levels of drug-metabolizing enzymes, potentially resulting in an alteration in the pharmacokinetics, therapeutic efficacy, and safety of drugs. This study investigated the hepatic cytochrome P450 (CYP) 2B1-modulating effect of a specific NAFLD state in dietary rat models. Sprague-Dawley rats were given a methionine/choline-deficient (MCD) or high-fat (HF) diet to induce NASH and SFL, respectively. The induction of these disease states was confirmed by plasma chemistry and liver histological analysis. Both the protein and mRNA levels of hepatic CYP2B1 were considerably reduced in MCD diet-fed rats; however, they were similar between the HF diet-fed and control rats. Consistently, the enzyme-kinetic and pharmacokinetic parameters for CYP2B1-mediated bupropion metabolism were considerably reduced in MCD diet-fed rats; however, they were also similar between the HF diet-fed and control rats. These results may promote a better understanding of the influence of NAFLD on CYP2B1-mediated metabolism, which could have important implications for the safety and pharmacokinetics of drug substrates for the CYP2B subfamily in patients with NAFLD.
[Mh] Termos MeSH primário: Bupropiona/administração & dosagem
Deficiência de Colina/tratamento farmacológico
Metionina/deficiência
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Colina/metabolismo
Deficiência de Colina/enzimologia
Deficiência de Colina/genética
Deficiência de Colina/metabolismo
Citocromo P-450 CYP2B1/genética
Citocromo P-450 CYP2B1/metabolismo
Dieta Hiperlipídica/efeitos adversos
Modelos Animais de Doenças
Seres Humanos
Fígado/efeitos dos fármacos
Fígado/metabolismo
Masculino
Hepatopatia Gordurosa não Alcoólica/enzimologia
Hepatopatia Gordurosa não Alcoólica/genética
Hepatopatia Gordurosa não Alcoólica/metabolismo
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
01ZG3TPX31 (Bupropion); AE28F7PNPL (Methionine); EC 1.14.14.1 (Cytochrome P-450 CYP2B1); N91BDP6H0X (Choline)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170407
[Lr] Data última revisão:
170407
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160621
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.6b01663


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[PMID]:27235785
[Au] Autor:Bátai-Konczos A; Veres Z; Szabó M; Ioja E; László G; Török G; Homolya L; Jemnitz K
[Ad] Endereço:Department of Functional Pharmacology, Institute of Organic Chemistry, Research Centre for Natural Sciences, HAS, 1117 Budapest, Magyar tudósok körútja 2, Hungary. Electronic address: flax84@gmail.com.
[Ti] Título:Comparative study of CYP2B1/2 induction and the transport of bilirubin and taurocholate in rat hepatocyte-mono- and hepatocyte-Kupffer cell co-cultures.
[So] Source:J Pharmacol Toxicol Methods;82:1-8, 2016 Nov - Dec.
[Is] ISSN:1873-488X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Hepatocyte-Kupffer cell (KC) co-cultures represent a promising approach for in vitro modeling of complex interactions between parenchymal and non-parenchymal cells in the liver, responsible for drug-induced liver injury (DILI). In this study we aimed to compare hepatocyte monocultures with hepatocyte-KC co-cultures regarding some basic liver functions associated with the chemical defense system. These pathways involve transporters and enzymes the function of which is highly sensitive towards hepatotoxic events. METHODS: CYP2B1/2 induction and the biliary and sinusoidal elimination of bilirubin (B) and taurocholate (TC) were studied in rat hepatocyte sandwich cultures compared with rat hepatocyte-KC sandwich co-cultures of 1:0, 6:1, 2:1 and 1:1 cell combinations representing the physiologic and pathologic conditions of the liver. RESULTS: KCs decreased phenobarbital inducibility of CYP2B1/2 in a cell ratio dependent manner and activation of KCs by lipopolisacharide (LPS) amplified this effect. Similarly, KCs decreased the transport of B and its glucuronides (BG) in both sinusoidal and canalicular directions resulting in its intracellular accumulation. In contrast, the uptake and the efflux of TC were greater in the co-cultures than in the hepatocyte monocultures. Immuno-labelling of sodium-dependent taurocholate transporter (Ntcp) revealed increased expression of the transporter in the presence of KCs. DISCUSSION: Here we presented that KCs have a direct impact on some hepatocyte functions suggesting that the co-culture model may be more suitable for drug related hepatotoxicity studies than hepatocyte monocultures.
[Mh] Termos MeSH primário: Hidrocarboneto de Aril Hidroxilases/biossíntese
Bilirrubina/metabolismo
Citocromo P-450 CYP2B1/biossíntese
Hepatócitos/enzimologia
Macrófagos do Fígado/enzimologia
Modelos Biológicos
Esteroide Hidroxilases/biossíntese
Ácido Taurocólico/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
Doença Hepática Induzida por Substâncias e Drogas/enzimologia
Doença Hepática Induzida por Substâncias e Drogas/metabolismo
Técnicas de Cocultura
Interações Medicamentosas
Indução Enzimática
Hepatócitos/efeitos dos fármacos
Macrófagos do Fígado/efeitos dos fármacos
Lipopolissacarídeos/farmacologia
Masculino
Desentoxicação Metabólica Fase I
Ratos
Ratos Wistar
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipopolysaccharides); 0 (lipopolysaccharide, E coli O55-B5); 5E090O0G3Z (Taurocholic Acid); EC 1.14.- (Steroid Hydroxylases); EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases); EC 1.14.14.1 (Cytochrome P-450 CYP2B1); EC 1.14.14.1 (steroid 16-beta-hydroxylase); RFM9X3LJ49 (Bilirubin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170515
[Lr] Data última revisão:
170515
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160529
[St] Status:MEDLINE


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[PMID]:27143372
[Au] Autor:Gulyaeva LF; Chanyshev MD; Kolmykov SK; Ushakov DS; Nechkin SS
[Ad] Endereço:Institute of Molecular Biology and Biophysics, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia.
[Ti] Título:[Effect of xenobiotics on microRNA expression in rat liver].
[So] Source:Biomed Khim;62(2):154-9, 2016 Mar-Apr.
[Is] ISSN:2310-6972
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Using bioinformatics analysis we selected microRNAs which could bind 3'-UTR-region of cytochrome P450 (CYP) genes. Three microRNA miR-21, -221, -222, their potential targets might be mRNA for CYP1A1, and two microRNA miR-143, miR-152 for CYP2B1 accordingly were selected for experimental verification. Expression level of these microRNAs in rat liver upon benzo(a)pyrene (BP), phenobarbital (PB), and DDT induction was determined using RT-qPCR method. In rats treated by both BP, and DDT the hepatic content of miR-21, -221, -222 significantly demonstrated a 2-3-fold decrease. The decrease in miR expression was accompanied by a considerable (5.5-8.7-fold) increase in the CYP1A1-mediated EROD activity. The expression of miR-143 remained unchanged after the PB treatment, while the expression of miR-152 increased by 2 times, however, the (10.5-fold) increase in PROD activity of CYP2B was much higher. In the DDT-treated liver PROD activity increased by 20 times, the expression of miR-152 didn't change, and the expression of miR-143 increased by 2 times. The bioinformatics analysis of interactions between microRNAs and targets showed that the studied miRs can potentially bind 3'-end of AhR, ESR1, GR, CCND1, PTEN mRNA. Thus, the expression profile of miR-21, -221, -222, -143, -152 might change under the xenobiotics exposure. In silico analysis confirmed, that microRNAs target not only cytochrome P450 mRNA but also other genes, including those involved in hormonal carcinogenesis, they also can be regulated with studied miRs.
[Mh] Termos MeSH primário: Fígado/efeitos dos fármacos
MicroRNAs/efeitos dos fármacos
Xenobióticos/farmacologia
[Mh] Termos MeSH secundário: Animais
Benzo(a)pireno/farmacologia
Citocromo P-450 CYP1A1/genética
Indutores do Citocromo P-450 CYP1A2/farmacologia
Citocromo P-450 CYP2B1/genética
DDT/farmacologia
Regulação da Expressão Gênica/efeitos dos fármacos
Fígado/fisiologia
Masculino
Fenobarbital/farmacologia
Ratos Wistar
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytochrome P-450 CYP1A2 Inducers); 0 (MicroRNAs); 0 (Xenobiotics); 3417WMA06D (Benzo(a)pyrene); CIW5S16655 (DDT); EC 1.14.14.1 (Cytochrome P-450 CYP1A1); EC 1.14.14.1 (Cytochrome P-450 CYP2B1); YQE403BP4D (Phenobarbital)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160504
[Lr] Data última revisão:
160504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160505
[St] Status:MEDLINE
[do] DOI:10.18097/PBMC20166202154


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[PMID]:26910668
[Au] Autor:Al-Qattan MM; Abd-Alwahed MM; Arafah M; Al-Qattan AM; Shier MK
[Ad] Endereço:Riyadh, Saudi Arabia From the Department of Surgery, the College of Medicine Research Center, and the Department of Pathology, King Saud University.
[Ti] Título:Expression of nAG and Prod-1 in Terminal Phalanx Amputation Stumps of Adult Mice: An Experimental Model of Bone Regeneration in Higher Vertebrates.
[So] Source:Plast Reconstr Surg;137(3):879-86, 2016 Mar.
[Is] ISSN:1529-4242
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: nAG and Prod-1 are proteins responsible for the regeneration of completely amputated limbs in salamanders (which are lower vertebrates). The purpose of this study was to introduce an experimental distal phalanx amputation model in mice (which are higher vertebrates) in which nAG and Prod-1 are expressed in the amputation stumps. METHODS: Sixteen mice with amputation of the distal two-thirds of the distal phalanx were used. One hind limb was used and the central three digits were amputated. Injection of nAG and Prod-1 plasmids was performed in the footpad twice weekly in experimental mice (n = 8), and injection of solution only (without the plasmids) was performed twice weekly in control mice (n = 8). RESULTS: nAG and Prod-1 were expressed in experimental stumps only. This expression results in quicker and more mature bone regeneration in experimental animals, and this was shown using histology and immune stains to osteocalcin (an osteoblast marker). Finally, quantitative mRNA showed a 21-fold increase of osteocalcin in experimental stumps compared with control stumps, and this was statistically significant. CONCLUSION: Injection of nAG and Prod-1 into the footpad will result in their expression in the distal amputation stumps, and this will enhance bone regeneration in the model described.
[Mh] Termos MeSH primário: Cotos de Amputação/patologia
Regeneração Óssea/efeitos dos fármacos
Citocromo P-450 CYP2B1/farmacologia
Proteínas/farmacologia
[Mh] Termos MeSH secundário: Amputação/métodos
Animais
Biomarcadores/metabolismo
Biópsia por Agulha
Citocromo P-450 CYP2B1/metabolismo
Modelos Animais de Doenças
Imuno-Histoquímica
Camundongos
Camundongos Endogâmicos
Proteínas/metabolismo
RNA/metabolismo
Distribuição Aleatória
Reação em Cadeia da Polimerase em Tempo Real/métodos
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (Proteins); 63231-63-0 (RNA); EC 1.14.14.1 (Cytochrome P-450 CYP2B1)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160225
[Lr] Data última revisão:
160225
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160225
[St] Status:MEDLINE
[do] DOI:10.1097/01.prs.0000479994.27126.4a


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[PMID]:26826176
[Au] Autor:Shah MB; Liu J; Huo L; Zhang Q; Dearing MD; Wilderman PR; Szklarz GD; Stout CD; Halpert JR
[Ad] Endereço:School of Pharmacy, University of Connecticut, Storrs, Connecticut (M.B.S., J.L., L.H., P.R.W., J.R.H.); Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California (Q.Z., C.D.S.); Department of Biology, University of Utah, Salt Lake City, Utah (M
[Ti] Título:Structure-Function Analysis of Mammalian CYP2B Enzymes Using 7-Substituted Coumarin Derivatives as Probes: Utility of Crystal Structures and Molecular Modeling in Understanding Xenobiotic Metabolism.
[So] Source:Mol Pharmacol;89(4):435-45, 2016 Apr.
[Is] ISSN:1521-0111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Crystal structures of CYP2B35 and CYP2B37 from the desert woodrat were solved in complex with 4-(4-chlorophenyl)imidazole (4-CPI). The closed conformation of CYP2B35 contained two molecules of 4-CPI within the active site, whereas the CYP2B37 structure demonstrated an open conformation with three 4-CPI molecules, one within the active site and the other two in the substrate access channel. To probe structure-function relationships of CYP2B35, CYP2B37, and the related CYP2B36, we tested the O-dealkylation of three series of related substrates-namely, 7-alkoxycoumarins, 7-alkoxy-4-(trifluoromethyl)coumarins, and 7-alkoxy-4-methylcoumarins-with a C1-C7 side chain. CYP2B35 showed the highest catalytic efficiency (kcat/KM) with 7-heptoxycoumarin as a substrate, followed by 7-hexoxycoumarin. In contrast, CYP2B37 showed the highest catalytic efficiency with 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC), followed by 7-methoxy-4-(trifluoromethyl)coumarin (7-MFC). CYP2B35 had no dealkylation activity with 7-MFC or 7-EFC. Furthermore, the new CYP2B-4-CPI-bound structures were used as templates for docking the 7-substituted coumarin derivatives, which revealed orientations consistent with the functional studies. In addition, the observation of multiple -Cl and -NH-π interactions of 4-CPI with the aromatic side chains in the CYP2B35 and CYP2B37 structures provides insight into the influence of such functional groups on CYP2B ligand binding affinity and specificity. To conclude, structural, computational, and functional analysis revealed striking differences between the active sites of CYP2B35 and CYP2B37 that will aid in the elucidation of new structure-activity relationships.
[Mh] Termos MeSH primário: Cumarínicos/química
Citocromo P-450 CYP2B1/química
Imidazóis/química
Modelos Moleculares
Xenobióticos/química
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação/fisiologia
Cumarínicos/metabolismo
Cristalografia por Raios X
Citocromo P-450 CYP2B1/metabolismo
Imidazóis/metabolismo
Estrutura Secundária de Proteína
Ratos
Relação Estrutura-Atividade
Xenobióticos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Coumarins); 0 (Imidazoles); 0 (Xenobiotics); 0 (coumarin 7); EC 1.14.14.1 (Cytochrome P-450 CYP2B1)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170403
[Lr] Data última revisão:
170403
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160131
[St] Status:MEDLINE
[do] DOI:10.1124/mol.115.102111



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