title: The effects of intermittent hypoxia on redox status, NF-κB activation, and plasma lipid levels are dependent on the lowest oxygen saturation.
abstract: Obstructive sleep apnea syndrome (OSAS) is described as repetitive obstructions of the upper airways during sleep, causing concomitant episodes of systemic hypoxia and associated cardiovascular and metabolic pathologies. The mechanisms generating these pathologies are controversial. Because recurrent hypoxia is the element of inadequate respiration that leads to the pathology, experimental models of OSAS consist in the exposure of the animals to intermittent hypoxia (IH) by cycling O2 percentages in their habitats. A proposed mechanism linking the IH of OSAS to pathologies is the increased production of reactive oxygen species (ROS). However, it has been argued that many patients seem to lack oxidative stress and that, to augment ROS in IH animals, intense hypoxia, seldom encountered in patients, has to be applied. To solve the controversy, we have exposed rats to two intensities of IH (cycles of 10 or 5% O2, 40s, and then 21% O2, 80s; 8h/day, 15 days). We then measured reduced and oxidized glutathione and lipid peroxide levels, aconitase and fumarase activities, and ROS-disposal enzyme activity in liver, brain, and lung. Liver levels of nuclear NF-κB-p65 and plasma C-reactive protein (CRP), as well as lipid levels, were also assessed. Lowest hemoglobin saturations were 91.7 ± 0.8 and 73.5 ± 1.4%. IH caused tissue-specific oxidative stress related to hypoxic intensity. Nuclear NF-κB-p65 and lipid content in the liver and CRP in the plasma all increased with IH intensity, as did both plasma triglycerides and cholesterol. We conclude that IH, even of moderate intensity, causes oxidative stress probably related to the pathologies encountered in OSAS patients.
authors.affiliation: Institute of Molecular Biology and Genetics, CSIC, Department of Biochemistry and Molecular Biology and Physiology, School of Medicine, University of Valladolid, 47005 Valladolid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Quintero
authors.affiliation: Institute of Molecular Biology and Genetics, CSIC, Department of Biochemistry and Molecular Biology and Physiology, School of Medicine, University of Valladolid, 47005 Valladolid, Spain.
authors.forename: María Del Carmen
authors.initials: MDC
authors.lastname: Gonzalez-Martin
authors.affiliation: Institute of Molecular Biology and Genetics, CSIC, Department of Biochemistry and Molecular Biology and Physiology, School of Medicine, University of Valladolid, 47005 Valladolid, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Vega-Agapito
authors.affiliation: Institute of Molecular Biology and Genetics, CSIC, Department of Biochemistry and Molecular Biology and Physiology, School of Medicine, University of Valladolid, 47005 Valladolid, Spain; CIBER Enfermedades Respiratorias, Institute of Salud Carlos III, 28029 Madrid, Spain.
authors.forename: Constancio
authors.initials: C
authors.lastname: Gonzalez
authors.affiliation: Institute of Molecular Biology and Genetics, CSIC, Department of Biochemistry and Molecular Biology and Physiology, School of Medicine, University of Valladolid, 47005 Valladolid, Spain; CIBER Enfermedades Respiratorias, Institute of Salud Carlos III, 28029 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Obeso
authors.affiliation: CIBER Enfermedades Respiratorias, Institute of Salud Carlos III, 28029 Madrid, Spain; Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona-IDIBAPS, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
authors.affiliation: Institute of Molecular Biology and Genetics, CSIC, Department of Biochemistry and Molecular Biology and Physiology, School of Medicine, University of Valladolid, 47005 Valladolid, Spain; CIBER Enfermedades Respiratorias, Institute of Salud Carlos III, 28029 Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Agapito
authors.affiliation: Institute of Molecular Biology and Genetics, CSIC, Department of Biochemistry and Molecular Biology and Physiology, School of Medicine, University of Valladolid, 47005 Valladolid, Spain; CIBER Enfermedades Respiratorias, Institute of Salud Carlos III, 28029 Madrid, Spain. Electronic address: sarayube@ibgm.uva.es.
authors.forename: Sara
authors.initials: S
authors.lastname: Yubero
mesh_terms: D000154:Aconitate Hydratase / Q000097:blood*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002097:C-Reactive Protein; D002374:Catalase / Q000096:biosynthesis; D015687:Cell Hypoxia; D005649:Fumarate Hydratase / Q000097:blood*; D005978:Glutathione / Q000097:blood; D008054:Lipid Peroxides / Q000097:blood; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000096:biosynthesis; D051996:Transcription Factor RelA / Q000096:biosynthesis
chemical_list: D008054:Lipid Peroxides; D008055:Lipids; D017382:Reactive Oxygen Species; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D002097:C-Reactive Protein; D002374:Catalase; D013482:Superoxide Dismutase; D005649:Fumarate Hydratase; D000154:Aconitate Hydratase; D005978:Glutathione; D010100:Oxygen
keywords: Free radicals; Intermittent hypoxia; Oxidative stress