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.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D015232:Dinoprostone; D005966:Glucuronidase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D066298:In Vitro Techniques; D054833:Isoindoles; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008163:Luminescent Measurements; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D016566:Organoselenium Compounds; D011458:Prostaglandins E / Q000096:biosynthesis; D012643:Selenium
D000893:Anti-Inflammatory Agents; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D011458:Prostaglandins E; C042986:ebselen; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D005966:Glucuronidase; D012643:Selenium; D015232:Dinoprostone