Effects of streptolysin O, polyriboinosinic-polyribocytidylic acid and combinations with cyclophosphamide on the hepatic arylamine N-acetyltransferase and cytochrome P450-dependent monooxygenases in rats.
There is evidence that immunostimulation depresses the function of various cytochrome P450 (CYP)-dependent monooxygenases but activates the arylamine N-acetyltransferase (NAT). Therefore, the effects of the synthetic immunostimulator polyriboinosinic-polyribocytidylic acid (plC, 8 mg/kg i.p.), of sublytic doses of the streptococcal toxin streptolysin O (SLO, 50 HU/kg i.v. for 5 d) and of the immunosuppressor cyclophosphamide (CP, 100 mg/kg i.p.) on NAT and some monooxygenases were studied in rat liver. It was also evaluated whether CP might antagonize the effects of plC and SLO on drug metabolism. SLO, plC and CP reduced CYP content and the activities of some monooxygenases. NAT was significantly inhibited by CP (given 5 d before sacrifice) but not by plC, SLO or CP when given 2 d before sacrifice. CP lacked any effect on NAT if it was administered prior to SLO. However, it deteriorated synergistically the inhibition of the monooxygenases caused by SLO and plC.
Walter
R
R
Department of Pharmacology, Ernst Moritz Arndt University, Greifswald, Germany.
Hadasová
E
E
Scheuch
E
E
Siegmund
W
W
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D001426:Bacterial Proteins; D003520:Cyclophosphamide / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011066:Poly C / Q000494:pharmacology*; D011068:Poly G / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects; D013301:Streptolysins / Q000494:pharmacology*
D001426:Bacterial Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D013301:Streptolysins; C025964:streptolysin O; D011068:Poly G; C008961:poly G-poly C; D011066:Poly C; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001191:Arylamine N-Acetyltransferase