title: Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain.
abstract: Acute hypoxia increases the formation of reactive oxygen species (ROS) in the brain. However, the effect of reoxygenation, unavoidable to achieve full recovery of the hypoxic organ, has not been clearly established. The aim of the present study was to evaluate the effects of exposition to acute severe respiratory hypoxia followed by reoxygenation on the evolution of oxidative stress and apoptosis in the brain. We investigated the effect of in vivo acute severe normobaric hypoxia (rats exposed to 7% O2for 6h) and reoxygenation in normoxia (21% O2for 24h or 48h) on oxidative stress markers, the antioxidant system and apoptosis in the brain. After respiratory hypoxia we found increased levels of HIF-1α expression, lipid peroxidation, protein oxidation and nitric oxide in brain extracts. Antioxidant defence systems such as superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GPx) and the reduced/oxidized glutathione (GSH/GSSG) ratio were significantly decreased in the brain. After 24h of reoxygenation, oxidative stress parameters and the anti-oxidant system returned to control values. Regarding the apoptosis parameters, acute hypoxia increased cytochrome c, AIF and caspase 3 activity in the brain. The apoptotic effect is greatest after 24h of reoxygenation. Immunohistochemistry suggests that CA3 and dentate gyrus in the hippocampus seem more susceptible to hypoxia than the cortex. Severe acute hypoxia increases oxidative damage, which in turn could activate apoptotic mechanisms. Our work is the first to demonstrate that after 24h of reoxygenation oxidative stress is attenuated, while apoptosis is maintained mainly in the hippocampus, which may, in fact, be the cause of impaired brain function.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Barcelona, Avda Diagonal, 643, 08028 Barcelona, Spain.
authors.forename: Debora
authors.initials: D
authors.lastname: Coimbra-Costa
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Barcelona, Avda Diagonal, 643, 08028 Barcelona, Spain.
authors.forename: Norma
authors.initials: N
authors.lastname: Alva
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Barcelona, Avda Diagonal, 643, 08028 Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Duran
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Barcelona, Avda Diagonal, 643, 08028 Barcelona, Spain. Electronic address: tcarbonell@ub.edu.
authors.forename: Teresa
authors.initials: T
authors.lastname: Carbonell
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Barcelona, Avda Diagonal, 643, 08028 Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Rama
mesh_terms: D062107:Advanced Oxidation Protein Products / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D062107:Advanced Oxidation Protein Products; D000975:Antioxidants; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D010100:Oxygen
keywords: Antioxidants; Apoptosis; Normobaric hypoxia; Oxidative stress; Reoxygenation