Inhibition of glutathione synthesis in the newborn rat: a model for endogenously produced oxidative stress
| Autor: | Ajey Jain, Alton Meister, William W. Frayer, Peter A. M. Auld, Einar Stole, Johannes Martensson |
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| Rok vydání: | 1991 |
| Předmět: |
Male
Aging medicine.medical_specialty Antioxidant Glutamate-Cysteine Ligase medicine.medical_treatment Oxidative phosphorylation Mitochondrion Biology medicine.disease_cause chemistry.chemical_compound Isomerism Methionine Sulfoximine Internal medicine medicine Animals Buthionine sulfoximine Buthionine Sulfoximine Cell damage chemistry.chemical_classification Reactive oxygen species Multidisciplinary Rats Inbred Strains gamma-Glutamyltransferase Glutathione medicine.disease Mitochondria Rats Endocrinology Animals Newborn Biochemistry chemistry Organ Specificity Female Oxidative stress Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 88:9360-9364 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.88.20.9360 |
| Popis: | A model for oxidative stress is described in which glutathione (GSH) synthesis is selectively blocked in newborn rats by administration of L-buthionine-(S,R)-sulfoximine (BSO). In this model, the normal endogenous physiological formation of reactive oxygen species is largely unopposed, and therefore oxidative tissue damage occurs; because GSH is used for reduction of dehydroascorbate, tissue ascorbate levels decrease. In lung there are decreased numbers of lamellar bodies and decrease of intraalveolar surfactant. Proximal renal tubular, hepatic, and brain damage also occur. A diastereoisomer of BSO that does not inhibit GSH synthesis, L-buthionine-R-sulfoximine, does not produce toxicity; this control experiment renders it unlikely that the observed effects of BSO are produced by the sulfoximine moiety itself. There is correlation between the decrease of mitochondrial GSH levels and mitochondrial and cell damage. Oxidative stress as evaluated by mitochondrial damage and mortality can be prevented by treatment with GSH esters or ascorbate. There is apparent linkage between the antioxidant actions of GSH and ascorbate. This model, which may readily be applied to evaluation of the efficacy of other compounds in preventing oxidative stress, offers an approach to study of other effects of GSH deficiency (e.g., on lipid metabolism, hematopoiesis), and closely resembles oxidative stress that occurs in certain human newborns and in other clinical states. |
| Databáze: | OpenAIRE |
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