EFFECT OF STREPTOLYSIN-O ON RAT HEPATIC ACETYL COENZYME-A - ARYLAMINEN-ACETYLTRANSFERASE AND CYTOCHROME-P-450 2B1 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. Strepto lysin-O (SLO), a thiol-activated (oxygen-labile) hemolytic and immune- stimulating exotoxin produced by group A streptococci, has been report ed 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-45 0-catalyzed tolbutamide hydroxylation and NAT activities toward PA (a substrate for NAT1), and p-aminobenzoic acid (a substrate for NAT2) wa s examined ex vivo. Subacute SLO (SIGMA: Chemical Company, St. Louis, MO) pretreatment (100 Hemolytic Units/kg/day, intraperitoneal, for 4 d ays) did not alter body weight, liver weight or cytosolic protein cont ent as compared with controls. SLO-pretreatment did not alter NAT acti vities measured ex vivo, nor was an alteration in tolbutamide hydroxyl ation observed. Pretreatment with an alternative SLO preparation (DIFC O Laboratories, Detroit, MT) also failed to alter the parameters of bo dy weight, liver weight or cytosolic protein content as compared with controls. While treated animals had significantly reduced microsomal p rotein content, SLO pretreatment failed to alter the enzyme activities measured. We conclude that SLO does not serve as a useful model immun ostimulant for mechanistic studies as it produces no consistent effect on drug metabolizing enzymes.