Base de dados : MEDLINE
Pesquisa : G07.690 [Categoria DeCS]
Referências encontradas : 2 [refinar]
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[PMID]:28350814
[Au] Autor:Kumar R; Mota LC; Litoff EJ; Rooney JP; Boswell WT; Courter E; Henderson CM; Hernandez JP; Corton JC; Moore DD; Baldwin WS
[Ad] Endereço:Biological Sciences, Clemson University, Clemson, SC, United States of America.
[Ti] Título:Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9/10/13-null mice.
[So] Source:PLoS One;12(3):e0174355, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model. Compensatory changes in CYP expression that occur in these models may also occur in polymorphic humans, or may complicate interpretation of ADME studies performed using these models. The loss of CAR causes significant changes in several CYPs probably due to loss of CAR-mediated constitutive regulation of these CYPs. Expression and activity changes include significant repression of Cyp2a and Cyp2b members with corresponding drops in 6α- and 16ß-testosterone hydroxylase activity. Further, the ratio of 6α-/15α-hydroxylase activity, a biomarker of sexual dimorphism in the liver, indicates masculinization of female CAR-null mice, suggesting a role for CAR in the regulation of sexually dimorphic liver CYP profiles. The loss of Cyp3a causes fewer changes than CAR. Nevertheless, there are compensatory changes including gender-specific increases in Cyp2a and Cyp2b. Cyp2a and Cyp2b were down-regulated in CAR-null mice, suggesting activation of CAR and potentially PXR following loss of the Cyp3a members. However, the loss of Cyp2b causes few changes in hepatic CYP transcript levels and almost no significant compensatory changes in protein expression or activity with the possible exception of 6α-hydroxylase activity. This lack of a compensatory response in the Cyp2b9/10/13-null mice is probably due to low CYP2B hepatic expression, especially in male mice. Overall, compensatory and regulatory CYP changes followed the order CAR-null > Cyp3a-null > Cyp2b-null mice.
[Mh] Termos MeSH primário: Hidrocarboneto de Aril Hidroxilases/genética
Sistema Enzimático do Citocromo P-450/genética
Família 2 do Citocromo P450/genética
Receptores Citoplasmáticos e Nucleares/genética
Esteroide Hidroxilases/genética
[Mh] Termos MeSH secundário: Animais
Hidrocarboneto de Aril Hidroxilases/metabolismo
Sistemas CRISPR-Cas
Sistema Enzimático do Citocromo P-450/metabolismo
Família 2 do Citocromo P450/metabolismo
Feminino
Deleção de Genes
Expressão Gênica
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Fenômenos Farmacológicos e Toxicológicos
Receptores Citoplasmáticos e Nucleares/metabolismo
Esteroide Hidroxilases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Cytoplasmic and Nuclear); 0 (constitutive androstane receptor); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.- (cytochrome P-450 2B13, mouse); EC 1.14.- (Steroid Hydroxylases); EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases); EC 1.14.14.1 (CYP3A protein, mouse); EC 1.14.14.1 (Cyp2b10 protein, mouse); EC 1.14.14.1 (Cyp2b9 protein, mouse); EC 1.14.14.1 (Cytochrome P450 Family 2)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0174355


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[PMID]:27986219
[Au] Autor:Birngruber T; Sinner F
[Ad] Endereço:Joanneum Research GmbH, HEALTH - Institute for Biomedicine and Health Sciences, Neue Stiftingtalstrasse 2, 8010 Graz, Austria. Electronic address: ca.health@joanneum.at.
[Ti] Título:Cerebral open flow microperfusion (cOFM) an innovative interface to brain tissue.
[So] Source:Drug Discov Today Technol;20:19-25, 2016 Jun.
[Is] ISSN:1740-6749
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cerebral open flow microperfusion (cOFM) is a new in-vivo technique for continuous sampling of the interstitial fluid in brain tissue. cOFM can be used to monitor substance transport across the blood-brain barrier (pharmacokinetics) and to investigate metabolic changes in brain tissue after drug application (pharmacodynamics). The possibility of long-term implantation into the brain makes cOFM an outstanding tool in the development of brain relevant pharmaceutics.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
Perfusão/métodos
[Mh] Termos MeSH secundário: Animais
Microtecnologia/instrumentação
Microtecnologia/métodos
Perfusão/instrumentação
Farmacocinética
Fenômenos Farmacológicos e Toxicológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161218
[St] Status:MEDLINE



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