Effect of p-xylene metabolites, p-methylbenzyl alcohol and 2,5-dimethylphenol, on rat hepatic and pulmonary microsomal metabolism.
Pulmonary metabolites of p-xylene, p-methylbenzyl alcohol (PMBA) and 2,5-dimethylphenol (DMP), were employed to investigate the divergent effects of p-xylene on pulmonary and hepatic metabolism. Rats were given PMBA, DMP, or 10% cremophore (control) ip daily for 3 days, and effects on hepatic and pulmonary microsomal metabolism were determined 12 hours later. Both PMBA and DMP mimic the decrease in pulmonary benzyloxyresorufin-O-debenzylase activity previously reported for p-xylene, but neither could account for the potent induction of cytochrome P450 in the liver. Only PMBA had a consistent effect on P450IIB apoprotein levels, decreasing them in both the liver and lung. These data suggest that PMBA may have a significant role in the inhibition of pulmonary P450 caused by p-xylene.
Day
B J
BJ
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907-1334.
Carlson
G P
GP
D000818:Animals; D001592:Benzyl Alcohols / Q000378:metabolism / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014992:Xylenes / Q000378:metabolism* / Q000494:pharmacology
D001592:Benzyl Alcohols; D014992:Xylenes; C031286:4-xylene; D003577:Cytochrome P-450 Enzyme System; C076463:4-methylbenzyl alcohol; C048893:2,5-xylenol