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| Noël,F.; Nascimento-Viana,J.B.; Romeiro,L.A.S.; Silva,R.O.; Lemes,L.F.N.; Oliveira,A.S.; Giorno,T.B.S.; Fernandes,P.D.; Silva,C.L.M.. |
| This study aimed to estimate the absorption, distribution, metabolism and excretion (ADME) properties and safety of LDT5, a lead compound for oral treatment of benign prostatic hyperplasia that has previously been characterized as a multi-target antagonist of α1A-, α1D-adrenoceptors and 5-HT1A receptors. The preclinical characterization of this compound comprised the evaluation of its in vitro properties, including plasma, microsomal and hepatocytes stability, cytochrome P450 metabolism and inhibition, plasma protein binding, and permeability using MDCK-MDR1 cells. De-risking and preliminary safety pharmacology assays were performed through screening of 44 off-target receptors and in vivo tests in mice (rota-rod and single dose toxicity). LDT5 is stable in... |
| Tipo: Info:eu-repo/semantics/article |
Palavras-chave: Benign prostatic hyperplasia; ADME; Safety; Permeability; CYP; Preclinical development. |
| Ano: 2016 |
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2016001200603 |
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| Da Costa,N. Meireles; Visoni,S.B.C.; Dos Santos,I.L.; Barja-Fidalgo,T.C.; Ribeiro-Pinto,L.F.. |
| 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... |
| Tipo: Info:eu-repo/semantics/article |
Palavras-chave: Maternal protein restriction; Offspring; CYP; Perinatal nutrition; Metabolic programming. |
| Ano: 2016 |
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2016001100603 |
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| Maciel,Marcos Euzébio; Oliveira,Fausto Koga; Propst,Gustavo Bonfim; Bicalho,Maria da Graça; Cavalli,Iglenir João; Ribeiro,Enilze Maria de Souza Fonseca. |
| Individual variability in xenobiotic metabolism has been associated with susceptibility to developing complex diseases. Genes involved in xenobiotic metabolism have been evaluated in association studies; the difficulty of obtaining accurate gene frequencies in mixed populations makes interpretation of the results difficult. We sought to estimate population parameters for the cytochrome P450 and glutathione S-transferase gene families, thus contributing to studies using these genes as markers. We describe the frequencies of six genes (CYP1A1, CYP2D6, CYP2E1, GSTM1, GSTT1, and GSTP1) and estimate population parameters in 115 Euro-descendants and 196 Afro-descendants from Curitiba, South of Brazil. PCR-based methods were used for genotyping, and statistical... |
| Tipo: Info:eu-repo/semantics/article |
Palavras-chave: CYP; GST; Population study. |
| Ano: 2009 |
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572009000400010 |
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