Iron-initiated tissue oxidation: lipid peroxidation, vitamin E destruction and protein thiol oxidation. Inhibition by a novel antioxidant, U-78517F.

Oxidative injury was initiated by addition of ferrous ammonium sulfate (FAS) to a suspension of whole rat brain homogenate in Krebs buffer. After FAS addition, tissue vitamin E dropped sharply over a 30-sec interval and then recovered marginally for 5 min. After 5 min, vitamin E levels dropped to a low and constant level.

Comparison of the efficacy of mechanistically different antioxidants in the rat hemorrhagic shock model.

Four pharmacological mechanisms for antagonizing free radical generation or reactions were compared in terms of their efficacy in attenuating hemorrhagic shock in rats. These included opposing superoxide generation by xanthine oxidase (e.g.

U-78517F: a potent inhibitor of lipid peroxidation with activity in experimental brain injury and ischemia.

U-78517F (2-[4-[2,6-di-(1-pyrrolidinyl)-4-pyridinyl)-1-piperazinyl] methyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol, dihydrochloride), which combines the antioxidant ring portion of alpha-tocopherol together with the amine of the previously described 21-aminosteroids (e.g., U-74006F), is a novel inhibitor of iron-catalyzed lipid peroxidation.

Sex differences in postischemic neuronal necrosis in gerbils.

Twenty-four hour postischemic neuronal necrosis was compared in male vs. female Mongolian gerbils subjected to a 3-h period of severe incomplete hemispheric ischemia produced by unilateral carotid occlusion. The incidence of stroke-prone males was 42.