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

被引:47
作者
Oesch, F. [1 ,2 ]
Fabian, E. [3 ]
Landsiedel, Robert [3 ]
机构
[1] Johannes Gutenberg Univ Mainz, Inst Toxicol, Obere Zahlbacherstr 67, D-55131 Mainz, Germany
[2] Oesch Tox Toxicol Consulting & Expert Opin GmbH &, Rheinblick 21, Wackernheim, Germany
[3] GV TB, Expt Toxicol & Ecol, Z470,BASF SE,Carl Bosch Str 38, D-67056 Ludwigshafen, Germany
关键词
Xenobiotic metabolism; Lung; Cytochrome P450; Phase II metabolism; Experimental animals; In vitro models; GLUTATHIONE-S-TRANSFERASE; BRONCHIAL EPITHELIAL-CELLS; PRECISION-CUT RAT; FLAVIN-CONTAINING MONOOXYGENASE; POLYCYCLIC AROMATIC-HYDROCARBONS; MICROSOMAL EPOXIDE HYDROLASE; MESSENGER-RNA EXPRESSION; PHASE-II ENZYMES; IN-SITU HYBRIDIZATION; DNA ADDUCT FORMATION;
D O I
10.1007/s00204-019-02602-7
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:3419 / 3489
页数:71
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