Drug Metabolism Studies Using Tracheo-Bronchial Epithelial Cells

Drug Metabolism Studies Using Tracheo-Bronchial Epithelial Cells 

In general, biotransformation reactions are beneficial in that they facilitate the elimination of xenobiotics from pulmonary tissues. Sometimes, however, the enzymes convert a harmless substance into a reactive form. For example, CYP-mediated oxidation often results in the generation of more reactive intermediates. Thus, many compounds that elicit toxic injury to the lung are not intrinsically pneumotoxic but cause damage to target cells following metabolic activation. A classic example of this is the activation of benzo(a)pyrene, which is a constituent of tobacco smoke and combustion products, and is 

Lung metabolism studies would greatly benefit from the availability of reliable in vitro experimental models that are able to reproduce biochemical and toxicological processes that occur in the human lung. Because of differences in the expression profiles of biotransformation enzymes between animal species, conclusions drawn from experimental animals may not be representative of what occurs in the human lung. 

Expression of P450 Enzymes in Tracheo-Bronchicd Mucosa and Cell Cultures 

The limited availability of suitable human tissue for experimental studies and the rather low CYP expression level in the human lung, compared to that found in rodents [111], have notably limited identification of the lung CYP isoforms. By means of RT-PCR, it has been possible to qualitatively demonstrate the presence of several CYP mRNAs in the human bronchial mucosa, namely CYP1A1, 2A6, 2B6, 2C, 2E1 and 3A5, whereas the expression of CYP1A2, 2D6, 3A4 and 3A7 could be detected only in some samples (Table 10.1) [109, 111, 112], Immunohistochemical analysis has shown the significant expression of CYP enzymes in different pulmonary cells including 

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