Effect of streptolysin-O-on rat hepatic acetyl coenzyme-A: arylamine N-acetyltransferase and cytochrome P-450 2B 1/2 activities ex vivo.
Numerous immunostimulants have been found to increase N-acetylation in vivo but are not associated with a similar increase in vitro. Streptolysin-O (SLO), a thiol-activated (oxygen-labile) hemolytic and immune-stimulating exotoxin produced by group A streptococci, has been reported to increase the metabolic rate constant for sulfamethazine in vivo and arylamine N-acetyltransferase (NAT) activity toward procainamide (PA) ex vivo. The effect of SLO pretreatment of rats on cytochrome P-450-catalyzed tolbutamide hydroxylation and NAT activities toward PA (a substrate for NAT1), and p-aminobenzoic acid (a substrate for NAT2) was examined ex vivo. Subacute SLO (SIGMA Chemical Company, St. Louis, MO) pretreatment (100 Hemolytic Units/kg/day, intraperitoneal, for 4 days) did not alter body weight, liver weight or cytosolic protein content as compared with controls. SLO-pretreatment did not alter NAT activities measured ex vivo, nor was an alteration in tolbutamide hydroxylation observed. Pretreatment with an alternative SLO preparation (DIFCO Laboratories, Detroit, MI) also failed to alter the parameters of body weight, liver weight or cytosolic protein content as compared with controls. While treated animals had significantly reduced microsomal protein content, SLO pretreatment failed to alter the enzyme activities measured. We conclude that SLO does not serve as a useful model immunostimulant for mechanistic studies as it produces no consistent effect on drug metabolizing enzymes.
Drobitch
R K
RK
Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, 48202, USA.
Divakaruni
P
P
Svensson
C K
CK
D000107:Acetylation; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D001426:Bacterial Proteins; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013301:Streptolysins / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D013301:Streptolysins; C025964:streptolysin O; D019362:Cytochrome P-450 CYP2B1; D001191:Arylamine N-Acetyltransferase