Effects of streptolysin O, picibanil (OK 432) and interferon alpha 2A on cytochrome P-450-dependent monooxygenases and arylamine N-acetyltransferase in rat liver.
Streptolysin O, a thiol-activated exotoxin from group A beta-haemolytic streptococci, caused a dose-dependent depression of aniline hydroxylase, aminopyrine N-demethylase and ethylmorphine N-demethylase activities when added into the hepatic microsomal mixtures from male rats at concentrations 0.02-0.4 HU/mL in vitro. The activities of 7-ethoxycoumarin O-deethylase, 7-ethylresorufin O-deethylase and 7-pentylresorufin O-depentylase were not altered with the used concentrations of the toxin. Specific antibody against haemolytic action of streptolysin O added to incubation mixtures in vitro was not able to protect streptolysin-sensitive monooxygenases from the inhibition. The addition of streptolysin O (0.01-0.8 HU/mL) into the cytosol-containing medium did not significantly influence the activity of procainamide N-acetyltransferase. Immunomodulators picibanil (OK 432) and human recombinant interferon alpha 2A which are known to suppress oxidative metabolism in vivo in humans and animals, were without effect either on the cytochrome P-450-dependent monooxygenases or on the N-acetyltransferase activity when administered in vitro at the doses real in their clinical application (0.001-0.1 KE/mL of picibanil and 10-500 U/mL of alpha-interferon).
Hadasová
E
E
Department of Pharmacology, Medical Faculty, Masaryk University, Czech Republic.
Siegmund
W
W
Walter
R
R
Scheuch
E
E
Franke
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors*; D001426:Bacterial Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D006461:Hemolysis / Q000187:drug effects / Q000276:immunology; D016898:Interferon-alpha / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D010844:Picibanil / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013301:Streptolysins / Q000276:immunology / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D016898:Interferon-alpha; D013301:Streptolysins; C025964:streptolysin O; D010844:Picibanil; D010105:Oxygenases; D001191:Arylamine N-Acetyltransferase