Effects of Interferon-γ and Streptolysin O On Hepatic Procainamide N-Acetyltransferase and Various Microsomal Cytochrome P450-Dependent Monooxygenases in Rats

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Abstract
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 immunstimu-lating doses of rat interferon-γ (IFNγ, 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 IFNγ and SLO activated NAT to 120% (P<0.05) and 135% (P<0.051, respectively. As expected, monooxygenases were depressed by IFNγ (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 IFNγ 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 IFNγ was abolished by actinomycin D and by the inhibitor of translation, cycloheximide. Obviously, SLO activated NAT independent of protein synthesis and different from IFNγ-mediated pathways. Posttranslational processes might be involved in NAT stimulation in the rats.