title: Mitochondrial glutathione and oxidative stress: implications for pulmonary oxygen toxicity in premature infants.
abstract: Administration of supplemental oxygen, despite being an important clinical therapy, can cause significant lung damage. Because they have underdeveloped lungs, prematurely born human infants frequently require supportive therapies that employ elevated oxygen concentrations, which put them at risk for developing pulmonary oxygen toxicity. This risk is made even greater by the immaturity of their cellular antioxidant defenses. Although the exact mechanisms of oxygen toxicity are still not fully defined, cellular damage is probably mediated by increased production of chemically reactive oxygen species (ROS) in the mitochondria. Cellular protection against ROS is provided by a variety of antioxidant molecules and enzymes, including the glutathione (GSH)-dependent antioxidant system. The GSH-dependent antioxidant enzyme system provides vital cellular protection against ROS, particularly hydrogen peroxide and certain organic hydroperoxides, under pathological and toxicological conditions, by using selenium-dependent and -independent peroxidases to reduce hydrogen peroxide or lipid peroxides to water or the respective alcohols, with the concurrent oxidation of GSH to glutathione disulfide (GSSG). In the mitochondria, limitations of GSH synthesis and transmembrane transport suggest that optimal functioning of the mitochondrial GSH system, and maintenance of adequate thiol-disulfide redox tone is essential to protect against the injurious effects of ROS. Manipulation of endogenous GSH concentrations can alter cellular responses to oxidant injury. Beneficial effects are evident when intracellular GSH concentrations are increased. In conditions that increase mitochondrial production of ROS, such as exposure to high concentrations of oxygen, therapies based on enhancing mitochondrial GSH concentrations could be highly beneficial.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. dodonovan@neo.bcm.tmc.edu
authors.forename: D J
authors.initials: DJ
authors.lastname: O'Donovan
authors.forename: C J
authors.initials: CJ
authors.lastname: Fernandes
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D005978:Glutathione; D010100:Oxygen