title: Oxidative stress in preterm rat brain is due to mitochondrial dysfunction.
abstract: Prematurity-mediated cerebral damage has been associated with oxidative stress. The aim of the present work was to study the possible role played by free oxygen radicals generated by mitochondrial respiratory function in cerebral injury in preterm neonates. Our results show that whereas total glutathione concentrations are similar in term and preterm neonates, the GSH/GSSG ratio decreases sharply in preterm neonates immediately after birth. This effect is not due to a lack of enzymes involved in GSH regeneration, such as glutathione reductase and glucose-6-phosphate dehydrogenase, but to a significant increase in free-radical generation in preterm rat brain as shown by the increase in lipoperoxidation. Because the mitochondrion is the main source of free radicals in the cell, mitochondrial respiratory function was studied in the brain of preterm neonates. Our results show that prematurity prevented the postnatal increases in complex II-III activity and ATP concentrations that occur in term neonates at 5 min after delivery. All these effects were counteracted by the oxygen supply, suggesting that the inhibition of mitochondrial function is caused by restricted oxygen availability. Consequently, cerebral damage associated with prematurity may be mediated by mitochondrial free-radical generation as a consequence of hypoxia undergone by preterm neonates at birth.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Sánchez-Alvarez
authors.forename: Angeles
authors.initials: A
authors.lastname: Almeida
authors.forename: José M
authors.initials: JM
authors.lastname: Medina
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005978:Glutathione