Xenobiotic-metabolizing enzymes in the canine respiratory tract

Airway epithelial surface is the primary target of airborne pollutants. To estimate the distribution of xenobiotic-metabolizing enzymes in the respira tory tract of dogs, epithelia from different airway sites of four animals w ere analyzed for metabolism of sulfite (sulfite oxidase) and formaldehyde ( formaldehyde dehydrogenase and aldehyde dehydrogenase). In addition, glutat hione S-transferases were assayed using several model substrates. Enzyme ac tivities were compared with those found in liver parenchyma. The activity o f sulfite oxidase was found to be comparable in nose, trachea, and proximal and medium bronchi, but appeared to be lower in lung parenchyma of most an imals. In contrast, hepatic sulfite oxidase activity of these animals was s ubstantially higher compared to that in airway epithelia. The activity of g lutathione-dependent formaldehyde dehydrogenase (FDH) appeared to be highes t in nose and lowest in distal bronchi, lung, and liver parenchyma. The dis tribution pattern of the glutathione-independent aldehyde dehydrogenase (Al dDH) in the respiratory tract was different from that of FDH. Levels of Ald DH were about 5- to 10-fold lower than those of FDH, suggesting that AldDH is of minor importance for pulmonary formaldehyde detoxification. With rega rd to ethanol detoxification by a class I alcohol dehydrogenase (ADH), no m easurable enzyme activity could be detected at most respiratory sites contr ary to the high activity found in liver parenchyma. Regarding glutathione S -transferases (GSTs), different distributions of enzyme activities were fou nd in the large and small airways when using three substrates. The 1-chloro -2,4-dinitrobenzene (CDNB)-related activities in the cytosolic fraction of the upper (nose, trachea) and lower airways (proximal, medium and distal br onchi) were higher than those in the microsomal fraction. Interestingly, th ere was no difference between CDNB-related activities in the cytosolic and microsomal fraction of the liver, Highest cytosolic activities were found i n the nose, and were comparable to those detected in the liver parenchyma. The cytosolic 1,2-dichloro-4-nitrobenzene (DCNB)-related activities in the nose, proximal bronchi, and lung parenchyma were appeared to be markedly hi gher than those in trachea and medium and distal bronchi, while the microso mal activities were not detectable at most respiratory sites. In contrast, distinctly higher activities were measured in both fractions of liver tissu e. Cytosolic 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP)-related activities were present in upper and lower airways including lung parenchyma at compa rable levels, while in liver tissue the mean activities were distinctly low er. No EPNP-related activities were found in the microsomal fractions. In c onclusion, most xenobiotic-metabolizing enzymes investigated in this study could be detected in epithelia of various respiratory sites. The most outst anding result revealed higher levels of FDH activity in the nose and downst ream to the medium bronchi in comparison to those found in the small airway s, lung, and liver tissue. Similarly, the EPNP-related CST exhibited a dist inctly higher activity at all respiratory sites compared to the activity in liver tissue, suggesting a different regulation of this enzyme in lung and liver.