Abstract
m-Xylene (1 g/kg, i.p., 1 h) was shown to decrease aryl hydrocarbon hydroxylase (AHH) activity, a detoxification pathway for benzo[ a]pyrene (BaP), in the rat lung. Inhibition was maximal at 1 g/kg, 1 h after treatment and was sustained for at least 24 h. Reduction in cytochrome P-450 activity in rat lung was also observed, while liver activity was unchanged. p-Xylene has been previously shown to produce a similar pattern of MFO changes in rat brain. The lipid composition of the microsomal membrane is important to mixed function oxidase (MFO) regulation and function. Since the xylenes are lipophilic, these compounds were studied to determine whether they alter pulmonary microsomal lipids. p-Xylene produced an organ specific increase in lipid peroxidation in the rat lung. This was accompanied by decreases in lung microsomal total phospholipid (PL) and phosphatidylcholine (PC) content. Pulmonary microsomal membrane fluidity was also reduced by p-xylene administration. In comparison, m-xylene administration did not change any of the lipid membrane parameters tested. These divergent results leave unresolved the role of altered PL metabolism in solvent-induced inhibition of MFO activity.
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