Abstract: Certain known and novel pyruvate derivatives are particularly active in restoring or preserving metabolic integrity in oxidatively competent cells that have been subjected to oxygen deprivation. These pyruvate-derived compounds include, but are not limited to oximes, amides, pyruvate analogues, modified pyruvate analogues, esters of pyruvate (e.g., polyol-pyruvate esters, pyruvate thioesters, glycerol-pyruvate esters and dihydroxyacetone-pyruvate esters). Such pyruvate derivatives (including single tautomers, single stereoisomers and mixtures of tautomers and/or stereoisomers, and the pharmaceutically acceptable salts thereof) are useful in the manufacture of pharmaceutical compositions for treating a number of conditions characterized by oxidative stress.

Abstract: Certain known and novel pyruvate derivatives are particularly active in restoring or preserving metabolic integrity in oxidatively competent cells that have been subjected to oxygen deprivation. These pyruvate-derived compounds include, but are not limited to oximes, amides, pyruvate analogues, modified pyruvate analogues, esters of pyruvate (e.g., polyol-pyruvate esters, pyruvate thioesters, glycerol-pyruvate esters and dihydroxyacetone-pyruvate esters). Such pyruvate derivatives (including single tautomers, single stereoisomers and mixtures of tautomers and/or stereoisomers, and the pharmaceutically acceptable salts thereof) are useful in the manufacture of pharmaceutical compositions for treating a number of conditions characterized by oxidative stress.

Abstract: Certain known and novel pyruvate derivatives are particularly active in restoring or preserving metabolic integrity in oxidatively competent cells that have been subjected to oxygen deprivation. These pyruvate-derived compounds include, but are not limited to oximes, amides, pyruvate analogues, modified pyruvate analogues, esters of pyruvate (e.g., polyol-pyruvate esters, pyruvate thioesters, glycerol-pyruvate esters and dihydroxyacetone-pyruvate esters). Such pyruvate derivatives (including single tautomers, single stereoisomers and mixtures of tautomers and/or stereoisomers, and the pharmaceutically acceptable salts thereof) are useful in the manufacture of pharmaceutical compositions for treating a number of conditions characterized by oxidative stress.

Abstract: Non-naturally-occuring compositions for use in amelioration of disruption of energy metabolism secondary to stress are described. The compositions comprise a tocopherol and/or a derivative thereof, and a synergist, and are particularly suited for use as nutritional supplements. Synergists include, but are not limited to, flavonoids and lactoferrin and/or derivatives thereof. Compositions comprising an optimized formulation comprising a tocopherol and an additional compound such as daidzein or biochanin A are also described. Methods of making these compositions and methods of ameliorating injury(ies) or disruption of energy metabolism secondary to stress, comprising administering such compositions, are also disclosed.

Abstract: Methods and compositions are provided for screening compounds for anti-stress activity. A rat hepatoma-derived cell line is employed, which is particularly responsive to mitochondrial function inhibiting agents, demonstrated by the extracellular release of lactate dehydrogenase and the formation of lactate. Cytoprotectant agents are shown to reverse the lactate dehydrogenase release in the presence of mitochondrial function interfering agents, as a model for the effects of hypoxia on cellular energetic function.

Abstract: Purine derivatives are provided for treatment of cellular stress, particularly hypoxia. By administering the purine derivatives by themselves or in conjunction with other compounds, particularly electron acceptor compounds and/or amino acids, the time for irreversible cellular changes, particularly mortality, can be greatly extended.