title: Simulating sleep apnea by exposure to intermittent hypoxia induces inflammation in the lung and liver.
abstract: Sleep apnea is a breathing disorder that results from momentary and cyclic collapse of the upper airway, leading to intermittent hypoxia (IH). IH can lead to the formation of free radicals that increase oxidative stress, and this mechanism may explain the association between central sleep apnea and nonalcoholic steatohepatitis. We assessed the level of inflammation in the lung and liver tissue from animals subjected to intermittent hypoxia and simulated sleep apnea. A total of 12 C57BL/6 mice were divided into two groups and then exposed to IH (n = 6) or a simulated IH (SIH) (n = 6) for 35 days. We observed an increase in oxidative damage and other changes to endogenous antioxidant enzymes in mice exposed to IH. Specifically, the expression of multiple transcription factors, including hypoxia inducible factor (HIF-1α), nuclear factor kappa B (NF-κB), and tumor necrosis factor (TNF-α), inducible NO synthase (iNOS), vascular endothelial growth factor (VEGF), and cleaved caspase 3 were shown to be increased in the IH group. Overall, we found that exposure to intermittent hypoxia for 35 days by simulating sleep apnea leads to oxidative stress, inflammation, and increased activity of caspase 3 in the liver and lung.
authors.affiliation: Ciências Médicas, Programa de Pós-Graduação em Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), 90035-903 Porto Alegre, RS, Brazil. darlanpr@yahoo.com.br
authors.forename: Darlan Pase
authors.initials: DP
authors.lastname: da Rosa
authors.forename: Luiz Felipe
authors.initials: LF
authors.lastname: Forgiarini
authors.forename: Diego
authors.initials: D
authors.lastname: Baronio
authors.forename: Cristiano Andrade
authors.initials: CA
authors.lastname: Feijó
authors.forename: Dênis
authors.initials: D
authors.lastname: Martinez
authors.forename: Norma Possa
authors.initials: NP
authors.lastname: Marroni
mesh_terms: D000818:Animals; D006505:Hepatitis / Q000209:etiology*; D000860:Hypoxia / Q000150:complications*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D018384:Oxidative Stress; D011014:Pneumonia / Q000209:etiology*; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II