A novel biologically active seleno-organic compound--III. Effects of PZ 51 (Ebselen) on glutathione peroxidase and secretory activities of mouse macrophages.

PZ 51 (2-phenyl-1,2-benzisoselenazol-3(2H)-on), a selenium-containing compound with glutathione peroxidase (GSH-Px)-like activity, was administered to selenium-deficient mice for 5 days. A significant increase in peritoneal macrophage GSH-Px activity after treatment was only observed when basal GSH-Px activity was almost zero (i.e. in 19 weeks selenium-deficient animals), possibly due to binding of PZ 51 to the macrophages. This indicates that PZ 51 releases very little, if any, free selenium for incorporation into endogenous GSH-Px. The compound in vitro exerted a concentration-dependent inhibition of the generation of chemiluminescence by resident mouse peritoneal macrophages and a partial inhibition of the production of prostaglandin E2 by resident peritoneal macrophages. beta-Glucuronidase production by C. parvum-activated peritoneal macrophages was unaffected by PZ 51. These in vitro data can be explained on the basis of a selective peroxide scavenging and/or GSH-Px-like activity of PZ 51, offering a novel approach to anti-inflammatory therapy.