Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

Oesch, F; Fabian, E; Landsiedel, R

HERO ID

7712847

Reference Type

Journal Article

Subtype

Review

Year

2019

Language

English

PMID

31673725

HERO ID 7712847
Material Type Review
In Press No
Year 2019
Title Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models
Authors Oesch, F; Fabian, E; Landsiedel, R
Journal Archives of Toxicology
Volume 93
Issue 12
Page Numbers 3419-3489
Abstract The xenobiotic metabolism in the lung, an organ of first entry of xenobiotics into the organism, is crucial for inhaled compounds entering this organ intentionally (e.g. drugs) and unintentionally (e.g. work place and environmental compounds). Additionally, local metabolism by enzymes preferentially or exclusively occurring in the lung is important for favorable or toxic effects of xenobiotics entering the organism also by routes other than by inhalation. The data collected in this review show that generally activities of cytochromes P450 are low in the lung of all investigated species and in vitro models. Other oxidoreductases may turn out to be more important, but are largely not investigated. Phase II enzymes are generally much higher with the exception of UGT glucuronosyltransferases which are generally very low. Insofar as data are available the xenobiotic metabolism in the lung of monkeys comes closed to that in the human lung; however, very few data are available for this comparison. Second best rate the mouse and rat lung, followed by the rabbit. Of the human in vitro model primary cells in culture, such as alveolar macrophages and alveolar type II cells as well as the A549 cell line appear quite acceptable. However, (1) this generalization represents a temporary oversimplification born from the lack of more comparable data; (2) the relative suitability of individual species/models is different for different enzymes; (3) when more data become available, the conclusions derived from these comparisons quite possibly may change.
Doi 10.1007/s00204-019-02602-7
Pmid 31673725
Wosid WOS:000494077700001
Url http://link.springer.com/10.1007/s00204-019-02602-7
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword Xenobiotic metabolism; Lung; Cytochrome P450; Phase II metabolism; Experimental animals; In vitro models