Effects of interferon-gamma and streptolysin O on hepatic procainamide N-acetyltransferase and various microsomal cytochrome P450-dependent monooxygenases in rats.
Immunostimulants known to initiate cytokine production were found to inhibit processes of microsomal drug oxidation but to activate arylamine N-acetylation. The present study investigated the effects of immunstimulating doses of rat interferon-gamma (IFN gamma, 670,000 units ip) and streptolysin O (SLO, 100 HU/kg iv for 5 days) on hepatic cytosolic N-acetyltransferase (NAT) and microsomal cytochrome P450 (CYP)-dependent monooxygenases in male Wistar rats. Both IFN gamma and SLO activated NAT to 120% (P < 0.05) and 135% (P < 0.05), respectively. As expected, monooxygenases were depressed by IFN gamma (P < 0.05) and SLO, the ethylresorufin O-deethylase being the most susceptible enzyme. The results suggested that not only the toxin of gram-positive streptococcal bacteria SLO, but also the cytokine IFN gamma can stimulate NAT activity in rat hepatic cytosol. While the enhancing SLO effect on NAT could not be neutralized by the inhibitor of transcription actinomycin D, NAT stimulation by IFN gamma was abolished by actinomycin D and by the inhibitor of translation, cycloheximide. Obviously, SLO activated NAT independent of protein synthesis and different from IFN gamma-mediated pathways. Posttranslational processes might be involved in NAT stimulation in the rats.
Walter
R
R
Department of Pharmacology, Medical Faculty of the Ernst-Moritz-Arndt University, Greifswald, Germany.
Siegmund
W
W
Scheuch
E
E
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000187:drug effects*; D001426:Bacterial Proteins; D003513:Cycloheximide / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000187:drug effects*; D003609:Dactinomycin / Q000633:toxicity; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D011342:Procainamide / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013301:Streptolysins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013379:Substrate Specificity
D001426:Bacterial Proteins; D013301:Streptolysins; C025964:streptolysin O; D003609:Dactinomycin; D007371:Interferon-gamma; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D001191:Arylamine N-Acetyltransferase; D011342:Procainamide