Search results for "CYP2E1"
showing 10 items of 36 documents
Effect of gene-gene and gene-environment interactions associated with antituberculosis drug-induced hepatotoxicity.
2017
This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene-gene and gene-environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires.We investigated 364 TB patients who received anti-TB drugs. Physicians collected demographic and clinical data to identify environmental risk factors for AT…
Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury
2017
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify…
Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and …
2020
The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELIS…
Cytochrome P-450 mRNA expression in human liver and its relationship with enzyme activity.
2001
CYP activity and protein contents have been measured in human liver using different techniques. In contrast, CYP mRNA data are scarce and the relationships between CYP mRNA contents and activities have not been established. These studies deserve further attention because mRNA determinations by RT-PCR require a very small amount of material (e.g., liver needle biopsy) and could provide important data regarding CYP expression regulation. In this study we measured in 12 human liver samples the mRNA contents of 10 CYPs by quantitative RT-PCR and the metabolic activities using specific substrates. mRNA contents and activities showed high correlation coefficients for CYP1A1, CYP1A2, CYP3A4, CYP2D…
Cytochrome P450 2E1 variable number tandem repeat polymorphisms and health risks: A genotype-phenotype study in cancers associated with drinking and/…
2012
Cytochrome P450 2E1 (CYP2E1) is one of the main enzymes involved in the oxidation of ethanol and in the transformation of a number of potentially dangerous compounds. It has various polymorphic sites, one of which is a variable number tandem repeat (VNTR) polymorphism previously described in the 5'-flanking region. The aim of this study was to investigate the genotype-phenotype association between CYP2E1 VNTR polymorphisms and risky health habits in healthy subjects and to analyze the associations between these polymorphisms with drinking- and/or smoking-related cancers. We analyzed 166 healthy subjects by genotyping for the CYP2E1 VNTR polymorphism associated with drinking and/or smoking h…
Interest of genotyping and phenotyping of drug-metabolizing enzymes for the interpretation of biological monitoring of exposure to styrene
2002
In the field of occupational and/or environmental toxicology, the measurement of specific metabolites in urine may serve to assess exposure to the parent compounds (biological monitoring of exposure). Styrene is one of the chemicals for which biological monitoring programs have been validated and implemented in environmental and occupational medicine. However, inter-individual differences in the urinary excretion exist both for the main end-products (mandelic acid and phenylglyoxylic acid) and for its specific mercapturic acids (phenylhydroxyethylmercapturic acids, PHEMA). This limits to a certain extent the use of these metabolites for an accurate assessment of styrene exposure. In a group…
Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells
2006
AIM: To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells (ADSC) and bone marrow-derived mesenchymal stem cells (BMSC) in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC. METHODS: BMSCs were obtained from patients undergoing total hip arthroplasty and ADSC from human adipose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver development using a 2-step protocol with sequ…
Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling
2014
The generation of excessive amounts of reactive oxygen species (ROS) leads to cellular oxidative stress that underlies a variety of forms of hepatocyte injury and death including that from alcohol. Although ROS can induce cell damage through direct effects on cellular macromolecules, the injurious effects of ROS are mediated largely through changes in signal transduction pathways such as the mitogen-activated protein kinase c-Jun N-terminal kinase (JNK). In response to alcohol, hepatocytes have increased levels of the enzyme cytochrome P450 2E1 (CYP2E1) which generates an oxidant stress that promotes the development of alcoholic steatosis and liver injury. These effects are mediated in larg…
POLIMORFISMI DEI GENI CYP2A6 E CYP2E1 IN RELAZIONE A STILI DI VITA IN UNA POPOLAZIONE DELLA SICILIA CENTRO-OCCIDENTALE
2008
Le più recenti stime dell’OMS testimoniano che le patologie correlate all’abitudine al fumo e al consumo di alcool sono tra le principali cause di morte nei soggetti adulti ed è noto che la diversità interindividuale nell’adottare tali stili di vita è attribuibile, oltre che a fattori psico-sociali, anche a polimorfismi dei geni per i citocromi P450. Questo studio mira a verificare se esista una correlazione fra i genotipi CYP2A6 -CYP2E1 e abitudine al fumo e consumo d’alcool nella Sicilia centro-occidentale. I risultati ottenuti dall’analisi della distribuzione di alcuni alleli di entrambi i geni in 65 soggetti (41 donne e 24 uomini) hanno evidenziato che i genotipi CYP2A6*1/*4A e CYP2A6*1…
Evaluation of Cytochrome P450 Activities in Human Hepatocytes In Vitro
2011
Major hepatic cytochrome P450 activities (CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) can be simultaneously examined in human hepatocytes by incubation with a cocktail of multiple specific probes. Cocktail strategy in combination with mass spectrometry is shown to be a robust, fast, and sensitive procedure for P450 activity assessment. This procedure allows a drastic reduction of the number of cells required in the assay and sample analysis time and increases throughput and reproducibility. Major applications of the probe cocktail strategy are P450 phenotyping of hepatocytes and induction studies.