FREE-RADICAL SCAVENGING ENZYME-ACTIVITY AND RELATED TRACE-METALS IN CLOZAPINE-INDUCED AGRANULOCYTOSIS - A PILOT-STUDY

We hypothesized that patients who had experienced clozapine-induced ag ranulocytosis would have abnormalities in their free radical scavengin g enzyme activity (FRESA) and levels of related trace metals. We there fore measured FRESA profiles and related trace metals in four groups: post-clozapine agranulocytosis (POST CLOZ AGRAN) (N = 9); clozapine no agranulocytosis (CLOZ NO AGRAN) (N = 12); West Coast controls (WC CON TROLS) (N = 14); and Long Island Jewish Medical Center controls (LIJ C ONTROLS) (N = 12). Glutathione peroxidase (GSH-Px, Pl) levels in plasm a were lowest in the POST CLOZ AGRAN group (34.3 +/- 6.9 IU/dl [standa rd deviation; SD]; p < 0.002); red blood cell glutathione peroxidase ( GSH-Px, RBC) was highest in the WC CONTROLS (38.7 +/- 4.7 IU/g hemoglo bin [Hgb]; p < 0.008); and selenium (SE) levels in plasma were lower i n both the POST CLOZ AGRAN group (111.6 +/- 14.7 ng/ml) and the CLOZ N O AGRAN group (115.0 +/- 17.8) than in the WC CONTROLS (142.5 +/- 18.3 ;p < 0.0006). SE was also lower in the POST CLOZ AGRAN group than in t he LIJ CONTROLS (129.1 +/- 21.6; p < 0.04). The presence of at least o ne of the following: (1) GSH-Px, Pl < 37.6 IU/dl; (2) GSH-Px, RBC < 31 .0 IU/g Hgb; or (3) SE < 112.4 ng/ml, distinguished POST CLOZ AGRAN su bjects from the WC CONTROLS, but not from the LIJ CONTROLS. Data from this cross-sectional pilot study suggest that abnormalities in the bod y's antioxidant defense system may be involved in the pathogenesis of clozapine-associated agranulocytosis. If confirmed in large-scale, pro spective studies, these preliminary findings have potential clinical a pplication in the screening and prophylaxis of clozapine agranulocytos is.