Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 13 de 13
Filter
1.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;49(11): e5238, 2016. graf
Article in English | LILACS | ID: lil-797893

ABSTRACT

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.


Subject(s)
Animals , Female , Rats , Cytochrome P-450 Enzyme System/metabolism , Diet, Protein-Restricted , Lactation/metabolism , Liver/enzymology , Aryl Hydrocarbon Hydroxylases/metabolism , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1A2/metabolism , Cytochrome P-450 CYP2B1/metabolism , Cytochrome P-450 CYP2E1/metabolism , Models, Animal , Rats, Wistar , Steroid Hydroxylases/metabolism , Time Factors
2.
Rev. chil. cardiol ; 30(3): 218-224, dic. 2011. ilus, tab
Article in Spanish | LILACS | ID: lil-627039

ABSTRACT

Antecedentes: La mayoría de los pacientes que reciben tratamientos con anticoagulantes orales por periodos prolongados presentan variabilidad en la respuesta. El acenocumarol es el anticoagulante oral más prescrito en nuestro país, es biotransformado principalmente por CYP2C9 e investigaciones recientes demuestran que la variante CYP2C9*2 es una de las responsables de la variabilidad de respuesta a acenocumarol. Objetivo: Determinar las diferencias en los parámetros farmacocinéticos de acenocumarol en voluntarios que presentan la variante alélica CYP2C9*2. Métodos: Se estudiaron 24 voluntarios sanos. La detección de genotipos se realizó mediante PCR-RFLP y los parámetros farmacocinéticos se obtuvieron mediante la concentración plasmática de acenocumarol usando un método validado para UPLC-MS/MS. Resultados: Del total de 24 voluntarios, 19 tenían el genotipo CYP2C9*1/*1 (wt/wt), 4 tenían genotipo CYP2C9*1/*2 (heterocigoto) y 1 voluntario tenía genotipo de CYP2C9*2/*2 (homocigoto recesivo). Los parámetros farmacocinéticos del acenocumarol no fueron significativamente diferentes entre los individuos con genotipo CYP2C9*2 y CYP2C9*1. Sin embargo, la farmacocinética de acenocumarol del individuo CYP2C9*2/*2 mostró diferencias relevantes con respecto a la observada en el grupo CYP2C9*1/*1 (tmáx aumentó 1,4 veces, ke disminuyó 1,8 veces y t1/2 aumentó 1,7 veces). Conclusión: La farmacocinética de acenocumarol en el individuo con el genotipo CYP2C9*2/*2 refleja una potencial relevancia de este polimorfismo en el tratamiento con acenocumarol.


Background: Most of the patients receiving anticoagulant therapy for extended periods show variability in their clinical response. Acenocumarol, the most commonly prescribed oral anticoagulant in our country, is biotransformed mainly through CYP2C9 and recent research shows that CYP2C9*2 variant is partly responsible for the variable response to ace-nocumarol. Aim: to determine pharmacokinetics parameters of acenocumarol in volunteers exhibiting the CYP2C9*2 polymorphic variant. Methods: Genotype detection was performed using PCR-RFLP and pharmacokinetics parameters were obtained from the acenocumarol concentrations, using a UPLC-MS/MS validated method. The project was approved by the institutional Ethics Committee of the University of Chile's Faculty of Medicine. Results: 19 out of 24 volunteers had the CYP2C9*1/*1 genotype, 4 the CYP2C9*1/*2 genotype (heterozygous) and 1 subject had the CYP2C9*2/*2 genotype (recessive homozygous). No statistically significant differences between acenocumarol pharmacokinetics parameters of CYP2C9*2 compared to those with normal variant, CYP2C9*1were observed.. However, a single individual with the CYP2C9*2/*2 genotype showed different phar-macokinetics parameters: tmáx and t1/2 were increased 1.4 and 1.7 times, respectively, and kc was 1.8 times lower compared to the group with the CYP2C9*1/*1 genotype. Conclusion: There are clear differences in genotype-dependent acenocoumarol pharmacokinetics in individuals with the CYP2C9*2/*2 genotype, reflecting a potential relevance of this polymorphism in anticoagulation with acenocumarol.


Subject(s)
Humans , Male , Female , Adult , Acenocoumarol/pharmacokinetics , Anticoagulants/pharmacokinetics , Aryl Hydrocarbon Hydroxylases/genetics , Genotype , Aryl Hydrocarbon Hydroxylases/metabolism , Pharmacogenetics , Real-Time Polymerase Chain Reaction
3.
Indian J Biochem Biophys ; 2007 Aug; 44(4): 209-15
Article in English | IMSEAR | ID: sea-27931

ABSTRACT

The effects of aqueous Azadirachta indica leaf extract (AAILE) on benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis, B(a)P-DNA adduct formation and certain parameters of carcinogen biotransformation system in mice have been reported earlier from our laboratory. In this study, the effects of AAILE on the enzymes of B(a)P biotransformation, which play crucial role in initiation of chemical carcinogenesis - aryl hydrocarbon hydroxylase (AHH) and uridinediphosphoglucuronosyltransferase (UDP-glucuronosyltransferase) have been evaluated in murine forestomach and liver. In addition, lipid peroxidation (LPO) levels in forestomach as well as liver and the activities of tissue injury marker enzymes - lactate dehydrogenase, aspartate aminotransferase and alkaline phosphatase in the serum have also been evaluated. Oral administration of AAILE (100 mg/kg body wt for 2 weeks) reduces the AHH activity and enhances the UDP-glucuronosyltransferase activity in both the tissues, suggesting its potential in decreasing the activation and increasing the detoxification of carcinogens. The LPO levels decrease upon AAILE treatment in the hepatic tissue, suggesting its antioxidative and hence anti-carcinogenic effects. Non-significant alterations have been observed in tissue injury marker enzymes upon AAILE treatment, suggesting its safety at the given dose. In conclusion, AAILE appears to modulate initiation phase of carcinogenesis and may be suggested as safe and an effective agent for chemoprevention.


Subject(s)
Alkaline Phosphatase/blood , Animals , Anticarcinogenic Agents/pharmacology , Aryl Hydrocarbon Hydroxylases/metabolism , Aspartate Aminotransferases/blood , Azadirachta/chemistry , Benzo(a)pyrene/toxicity , Carcinogens , Cell Transformation, Neoplastic/chemically induced , Ganglioside Galactosyltransferase/metabolism , L-Lactate Dehydrogenase/blood , Lipid Peroxidation/drug effects , Liver/enzymology , Mice , Plant Extracts/pharmacology , Plant Leaves/chemistry , Stomach/enzymology , Stomach Neoplasms/chemically induced
4.
Rev. méd. Chile ; 134(4): 499-515, abr. 2006. ilus, tab
Article in Spanish | LILACS | ID: lil-428552

ABSTRACT

Pharmacogenetics is the study of genetically determined variations in the response to drugs and toxic agents, and their implications on disease. Recently, the discipline has acquired great relevancy due to the development of non-invasive molecular techniques that identify genetic variants in human beings. There is also a need to explain the individual differences in susceptibility to drug actions and disease risk. Genetic variants can modify the magnitude of a pharmacologic effect, toxicity threshold, secondary effects and drug interactions. There are approximately thirty families of drug-metabolizing enzymes with genetic variants that cause functional alterations and variations in pharmacologic activity. We summarize the general knowledge about genetic variants of biotransformation enzymes, their relationship with cancer risk and the role of ethnicity. Cancer pharmacogenetics is another promising and exciting research area that will explain why people with an almost identical group of genes, have a different susceptibility to cancer, whose etiology has genetic and environmental components.


Subject(s)
Humans , Aryl Hydrocarbon Hydroxylases/genetics , Genetic Predisposition to Disease/genetics , Neoplasms/genetics , Pharmacogenetics , Polymorphism, Genetic/genetics , Xenobiotics/metabolism , Aryl Hydrocarbon Hydroxylases/metabolism , Biotransformation/genetics , /genetics , /metabolism , /genetics , /metabolism , Ethnicity/genetics , Gene Frequency/genetics , Genotype , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Neoplasms/enzymology
5.
Arq. bras. cardiol ; Arq. bras. cardiol;85(supl.5): 9-14, out. 2005. tab, graf
Article in Portuguese | LILACS | ID: lil-418867

ABSTRACT

As estatinas são agentes hipolipemiantes que exercem os seus efeitos através da inibição da HMG-CoA redutase, enzima fundamental na síntese do colesterol, levando a uma redução do colesterol tecidual e um conseqüente aumento na expressão dos receptores de LDL. Existem consideráveis diferenças entre as estatinas, no que tange às propriedades farmacocinéticas, bem como ao coeficiente de hidrofilicidade, via hepática de metabolização (especialmente, do citocromo P450 e isoenzimas), meia-vida plasmática e eficácia na redução lipídica. As estatinas também podem diferir na capacidade de interação com outras drogas que utilizam a mesma via de metabolização. Recentemente, muitos efeitos pleiotrópicos têm sido relatados com estas drogas, bem como propriedades antiinflamatórias, melhora na função endotelial e benefícios na hemostasia.


Subject(s)
Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics , Cholesterol, LDL/metabolism , Drug Interactions , Muscular Diseases/chemically induced , Liver Diseases/chemically induced , Aryl Hydrocarbon Hydroxylases/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry , Rhabdomyolysis/chemically induced
6.
Indian J Exp Biol ; 1989 Sep; 27(9): 799-801
Article in English | IMSEAR | ID: sea-63251

ABSTRACT

A study was undertaken to investigate the activities of certain enzymes of drug metabolism in zinc deficiency. For this purpose, an experimental model for zinc deficiency was produced in a NIN/Wistar strain of rats by feeding an egg albumin-starch based diet. Of the two enzymes of Phase I pathway of drug metabolism studied, Benz (alpha) pyrene hydroxylase was altered in zinc deficiency and food restriction; the other one microsomal epoxide hydrolase was unchanged. The activity of glutathione-S-transferase, a key enzyme in conjugation reaction was significantly lowered in zinc deficiency as well as food restriction. These alterations in the activities of xenobiotic metabolising enzymes are discussed with reference to toxicity manifestation in zinc deficiency.


Subject(s)
Animals , Aryl Hydrocarbon Hydroxylases/metabolism , Benzopyrene Hydroxylase/metabolism , Epoxide Hydrolases/metabolism , Glutathione Transferase/metabolism , Rats , Rats, Inbred Strains , Zinc/blood
SELECTION OF CITATIONS
SEARCH DETAIL