Inhibition of XXXX respiratory-tract @entity1447 isozymes following inhalation of m-Xylene: possible role of metabolites.

@entity1447 @entity72243 @entity11574 @entity137 @entity72244 @entity18683 @entity35 @entity8019
@entity11574 is used as a solvent in paints, cleaning agents, and @entity18683 . Exposure occurs primarily by inhalation. The volatility and lipophilicity of the xylenes make the lung and nasal mucosa the primary target organs. m-Xylene (m-XYL) has been shown to alter @entity1447 ( @entity1447 ) activity in an organ- and isozyme-specific manner. The purpose of this work was to determine if the metabolism of m-XYL to the inhibitory metabolite m- @entity72243 (m- @entity8019 ) is the cause of inhibition of @entity1447 isozymes following in vivo inhalation exposure to m-XYL (100, 300 ppm), @entity72244 ( @entity72244 ) (50, 100 ppm), or m- @entity8019 (50, 100 ppm). A single 6-h inhalation exposure of @entity35 to m-XYL inhibited pulmonary CYPs 2B1, 2E1, and 4B1 in a dose-dependent manner. Inhalation of @entity72244 inhibited pulmonary CYPs 2B1 and 4B1 in a dose-dependent manner. m- @entity8019 inhibited pulmonary CYPs 2B1 and 2E1 in a dose-dependent manner, while 4B1 activity was increased dose dependently. Nasal mucosa @entity1447 2B1 and 2E1 activity was inhibited following exposure to m-XYL dose dependently, @entity72244 inhibited nasal mucosa CYPs 2E1 and 4B1 dose dependently. CYPs 2B1, 2E1, and 4B1 were inhibited in a dose-dependent fashion following inhalation of m- @entity8019 . Following high-performance liquid chromatography (HPLC) analysis, m- @entity8019 was detected after in vivo exposure to m-XYL, m- @entity8019 , and @entity72244 in a dose-dependent manner, with highest m- @entity8019 levels in the nasal mucosa and lung. Alteration of @entity1447 activity by m-XYL could result in increased or decreased @entity137 , changing the metabolic profiles of xenobiotics in coexposure scenarios in an organ-specific manner.
