Dose-related effects of m-xylene inhalation on the xenobiotic metabolism of the rat.
1. Male Wistar rats were exposed for two weeks (6 h/d, 5 d/week) to 0, 50, 400 or 750 p.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 (less than or equal to 1.2-fold), O-deethylation reactions (less than or equal to 1.8-fold) and UDP-glucuronosyltransferase activity (less than or equal to 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 (less than or equal to 1.3-fold), O-deethylation activity (less than or equal to 5.3-fold) and the rate of glucuronidation (less than or equal to 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.
D000273:Adipose Tissue / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014992:Xylenes / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D014992:Xylenes; D000410:Alanine Transaminase; C031285:3-xylene