Linked Life Data

17584020

Source:http://linkedlifedata.com/resource/pubmed/id/17584020

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-6-22
pubmed:abstractText
The aim of the present study was to develop and improve methods for phenotyping of CYP2E1, an important enzyme in the biotransformation of many industrial chemicals, therapeutic drugs and endogenous substances. The possibility to measure CYP2E1 activity in lymphocytes by using p-nitrophenol as a substrate and CYP2E1 protein levels by flow cytometry were studied in vitro. Further, the conventional chlorzoxazone method for in vivo phenotyping was studied by adjusting the dose to body weight in 10 healthy volunteers. Finally, the possibility to obtain the chlorzoxazone metabolic ratio in saliva samples was investigated. No CYP2E1 protein in lymphocytes was detected by using flow cytometry. Some enzyme activity was found in the experiments with p-nitrophenol, however, it could not be verified that it was catalyzed by CYP2E1. Chlorzoxazone and 6-hydroxychlorzoxazone were not detectable in saliva samples. The present in vivo experiments, combined with our previous data (in total 356 experiments in 50 subjects) show that the metabolic ratio increases with decreasing absorbed dose, expressed as the sum of chlorzoxazone and 6-hydroxychlorzoxazone in plasma at 2 h. The increase becomes pronounced at sum concentrations below 100 microM. In conclusion, chlorzoxazone metabolism in vivo remains the only available method for CYP2E1 phenotyping. The administered dose as well as the absorption of the probe influences the chlorzoxazone ratio. We suggest that a dose of 10 mg chlorzoxazone per kg body weight is used to estimate the CYP2E1 phenotype. Further, metabolic ratios should be disregarded if the sum of plasma chlorzoxazone and 6-hydroxychlorzoxazone is below 100 microM (blood sampled after 2 h).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1389-2002
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
493-8
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Phenotyping of cytochrome P450 2E1 in vitro and in vivo.
pubmed:affiliation
Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Lena.Ernstgard@ki.se
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't