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Two representative compounds from a novel chemical series of potent inhibitors of lipid peroxidation are described. The compounds 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha-methylpregna-1,4,9(11)-triene-3,20-dione monomethane sulfonate (U74006F) and 21-[4-(3,6-bis(diethylamino)-2-pyridinyl)-1-piperazinyl]-16(More)
Oxidation of Fe2+ in solution was dependent upon medium composition and the presence of lipid. The complete oxidation of Fe2+ in 0.9% saline was markedly accelerated in the presence of phosphate or EDTA and the ferrous oxidation product formed was readily recoverable as Fe2+ by ascorbate reduction. In contrast, in the presence of either brain synaptosomal(More)
Cattle had severe signs of toxicosis when gavaged dried ground Thermopsis montana (false lupine, poison bean, mountain thermopsis) at doses of 0.6-2.8 g/kg/day in a water suspension. Signs included depression, anorexia, swollen eye lids, arched back, tucked abdomen, rough hair coat, and in extremis a prolonged recumbency lasting up to 9 days. Plant potency(More)
Intense lipid peroxidation of brain synaptosomes initiated with Fenton's reagent (H2O2 + Fe2+) began instantly upon addition of Fe2+ and preceded detectable OH. formation. Although mannitol or Tris partially blocked peroxidation, concentrations required were 10(3)-fold in excess of OH. actually formed, and inhibition by Tris was pH dependent. Lipid(More)
Attachment of various iron chelating moieties to hydrophobic steroids greatly enhanced their abilities to inhibit iron-dependent lipid peroxidation. Using whole rat brain homogenates, lipid peroxidation initiated by the addition of 200 microM Fe2+ was assessed by the formation of thiobarbituric acid reactive products (TBAR). Under these conditions, 50%(More)
The interactions between lipid peroxidation and calcium in mediating damage to central nervous system membranes have been examined in several in vitro systems. Using isolated rat brain synaptosomes, brain mitochondria, or cultured fetal mouse spinal cord neurons, Ca2+ was found to markedly enhance lipid peroxidation-induced disruption of membrane function.(More)
The compound U74006F (21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha-methyl- pregna-1,4,9(11)-triene-3,20-dione) is one of a novel series of 21-aminosteroids that are potent inhibitors of iron-dependent lipid peroxidation. Chronic (4-6 days) dosing of mice or rats with high doses of U74006F (30-200 mg/kg/day) has indicated that the(More)
A case of malignant teratoma arising within a dysgenetic gonad in a 21-year-old phenotypic female with a 46 XY karyotype is presented. Admixtures of dysgerminoma, yolk sac tumor in close juxtaposition to embryoid bodies and elements of choriocarcinoma were also present. The contralateral gonad was an unidentifiable fibrovascular streak. Neither(More)