Depression of hepatic drug metabolism in endotoxin-treated and sarcoma-bearing mice.
The effect of a single dose of bacterial endotoxin (lipopolysaccharide, LPS) was compared with that of tumor implantation in mice on the activity of several hepatic cytochrome P-450-dependent monooxygenases. These included ethoxycoumarin O-deethylase, p-nitrophenol hydroxylase, aminopyrine N-demethylase, pentoxyresorufin O-depentylase, ethoxyresorufin O-deethylase and testosterone hydroxylase. For this purpose, mice were treated i.p. with 5 micrograms of LPS or implanted in the right paw with S 180 sarcoma. A comparable depression (30-50%) of total microsomal P-450 content as well as of the different P-450 monooxygenase activities tested was observed in LPS-treated mice (24 h after LPS) and in tumor bearing mice (12 days after implantation). The lack of differences in the pattern of depression of microsomal enzymes between LPS-treated and tumor-bearing mice suggests that a common mechanisms might be involved in the depression of P-450 by LPS or S-180 implantation.
Bertini
R
R
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Gervasi
P G
PG
Longo
V
V
Ghezzi
P
P
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003864:Depression, Chemical; D004435:Eating / Q000187:drug effects; D004926:Escherichia coli / Q000378:metabolism*; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012510:Sarcoma 180 / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism
D008070:Lipopolysaccharides; D004364:Pharmaceutical Preparations; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases