Search results for " CYP2E1"
showing 7 items of 17 documents
Differential modulation of CYP2E1 activity by cAMP-dependent protein kinase upon Ser129 replacement.
1998
Many toxic compounds are activated by cytochrome P450 (CYP) 2E1 to reactive metabolites, which represents a potential hazard for cellular homeostasis. Therefore knowledge about CYP2E1 regulation could be of great biological importance. It has been shown that CYP2E1 is controlled transcriptionally and post-translationally by phosphorylation. In the present study we investigated the role of serine-129 (Ser129) in the protein kinase A (PKA) recognition sequence motif Arg-Arg-Phe-Ser129. To gain further insights into the possible relevance of Ser129 for CYP2E1 function, Ser129 was replaced by alanine (Ala) or glycine (Gly) by site-directed mutations of the cDNA coding for CYP2E1. The mutant cDN…
Liver subcellular fractions from rats treated by organosulfur compounds from Allium modulate mutagen activation
2000
The effects of in vivo administration of naturally occurring organosulfur compounds (OSCs) from Allium species were studied on the activation of several mutagens. Male SPF Wistar rats were given p.o. one of either diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) or dipropyl disulfide (DPDS) during 4 consecutive days and the ability of hepatic S9 and microsomes from treated rats to activate benzo[a]pyrene (BaP), cyclophosphamide (CP), dimethylnitrosamine (DMN), N-nitrosopiperidine (N-PiP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was determined in the Ames test. Administration of DAS, DPS and DPDS resulted in a significant increase of the activation of…
Carcinogenic Etheno DNA Adducts in Alcoholic Liver Disease: Correlation with Cytochrome P-4502E1 and Fibrosis.
2017
BACKGROUND One mechanism by which alcoholic liver disease (ALD) progresses is oxidative stress and the generation of reactive oxygen species, among others due to the induction of cytochrome P-4502E1 (CYP2E1). Experimental data underline the key role of CYP2E1 because ALD could be partially prevented in rats by the administration of the specific CYP2E1 inhibitor chlormethiazole. As CYP2E1 is linked to the formation of carcinogenic etheno DNA adducts in ALD patients, a causal role of alcohol-induced CYP2E1 in hepatocarcinogenesis is implicated. The purpose of this study was to investigate CYP2E1 induction in ALD, and its correlation with oxidative DNA lesions and with hepatic histology. METHO…
Brain metabolism of ethanol and alcoholism: an update.
2007
It has long been suggested that some of the neuropharmacological, neurochemical and behavioural effects of ethanol are mediated by its first metabolite, acetaldehyde. In spite of the well documented psychoactivity of acetaldehyde, the precise role of this compound in alcohol abuse remains a matter of intense debate among scientists devoted to the study of alcoholism. Very frequently, the main drawback has been related to the presence of adequate levels of acetaldehyde or its derivatives inside the brain after ethanol ingestion. Since penetration into the central nervous system from blood of peripherically derived acetaldehyde is very low due to the high aldehyde dehydrogenase activity at th…
Effects of garlic powders with varying alliin contents on hepatic drug metabolizing enzymes in rats
2003
International audience; The anticarcinogenic effect of garlic has been demonstrated in both epidemiologic and experimental studies. In this study, possible mechanisms involved in the anticarcinogenic effect of garlic consumption were assessed by determining its capacity to alter drug metabolizing enzymes, in relation with its alliin content. Rats were fed a diet for 2 weeks containing 5% garlic powders produced from bulbs grown on soils with different levels of sulfate fertilization and therefore containing differing amounts of alliin. Activities of several hepatic enzymes, which are important in carcinogen metabolism such cytochromes P450 (CYP) and phase II enzymes, were determined. Garlic…
Farmacogenética de la Tuberculosis: Nuevo modelo de predicción de hepatotoxicidad inducida por fármacos antituberculosis
2017
Introducción: La hepatotoxicidad inducida por fármacos antituberculosis (HIFA) es una reacción adversa grave y potencialmente fatal del tratamiento de la tuberculosis (TB). Tres de los cuatro fármacos utilizados como terapia de primera línea (isoniacida, rifampicina, pirazinamida), han sido asociados a HIFA. Estudios sobre farmacogenética de la TB han asociado el desarrollo de HIFA con variaciones en genes de enzimas que metabolizan estos fármacos. Objetivos: Debido a que en Argentina la TB es una enfermedad re-emergente y a la elevada prevalencia de HIFA encontrada en pacientes internados, nos propusimos evaluar la posible asociación de factores ambientales y variantes genéticas en enzimas…
Variable Number of Tandem Repeats (VNTR) gene polymorphism of CYP2E1 in patients with pancreatic adenocarcinoma
2010
Context: The genetic polymorphism is considered a major source of variability, influencing the levels of gene expression. Cytochrome P450 2E1 (CYP2E1) is a mixed-function oxidase involved in the metabolism of the many endogenous and exogenous substances (ethanol, chemical carcinogens) in the hepatic and pancreatic tissue. CYP2E1 gene polymorphisms can cause various abilities of metabolize xenobiotic substances within a population with consequent increased susceptibility to various diseases,including cancer. One of the polymorphisms of the CYP2E1 gene is a VNTR (Variable Number Tandem Repeat) of some sequences in its "5 '- flanking region. Method : VNTR genotype CYP2E1 was determined by RFLP…