Dose-related effects ofm-xylene inhalation on the xenobiotic metabolism of the rat

Publisher Website
Google Scholar
Abstract
1. Male Wistar rats were exposed for two weeks (6h/d, 5d/week) to 0, 50, 400 or 750p.p.m. of m-xylene vapour in the air. 2. Microsomal enzyme activities were significantly increased in the liver as follows: NADPH-cytochrome c reductase (≤1·2-fold), O-deethylation reactions (≤1·8-fold) and UDP-glucuronosyltransferase activity (≤2·9-fold). Cytochrome P-450 concentrations also increased with dose. 3. Microsomal affinity to m-xylene increased with dose of m-xylene in vivo, similar to the increased affinity seen in type I spectra390–420nm formation with cytochrome P-450 in vitro. 4. Reduced glutathione concn. in liver declined significantly, while in the kidneys the glutathione remained unchanged. 5. In the kidneys, the concn. of cytochrome P-450 (≤1·3-fold), O-deethylation activity (≤5·3-fold) and the rate of glucuronidation (≤1·8-fold) increased with the dose of xylene. 6. Microsomal protein contents in liver and kidneys increased with the two highest doses of xylene. 7. The hepatic and renal effects were dose-dependent and closely related to the accumulation of m-xylene in perirenal fat. 8. Despite stimulation of xenobiotic metabolism by m-xylene, inhalation did not alter the serum transaminase activity or cause morphological changes in the liver.