Antioxidants inhibit the inflammatory and apoptotic processes in an intermittent hypoxia model of sleep apnea.
BACKGROUND
Sleep apnea causes intermittent hypoxia (IH). We aimed to investigate the proteins related to oxidative stress, inflammation and apoptosis in liver tissue subjected to IH as a simulation of sleep apnea in conjunction with the administration of either melatonin (MEL, 200 μL/kg) or N-acetylcysteine (NAC, 10 mg/kg).


METHODS
Seventy-two adult male Balb-C mice were divided: simulation of IH (SIH), SIH + MEL, SIH + NAC, IH, IH + MEL and IH + NAC. The animals were subjected to simulations of sleep apnea for 8 h a day for 35 days. The data were analyzed with ANOVA and Tukey tests with the significance set at p < 0.05.


RESULTS
In IH, there was a significant increase in oxidative stress and expression of HIF-1a. In addition, we observed increase in the activation levels of NF-kB. This increase may be responsible for the increased expression of TNF-alpha and iNOS as well as the significant increase of VEGF signaling and expression of caspase-3 and caspase-6, which suggests an increase in apoptosis. In the groups treated with antioxidants, the analysis showed that the enzyme activity and protein levels were similar to those of the non-simulated group.


CONCLUSIONS
Thus, we show that IH causes liver inflammation and apoptosis, which may be protected with either MEL or NAC.
Programa de Pós-Graduação Medicina, Ciências Médicas, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, CEP 90670-001, Brazil, darlanpr@yahoo.com.br.
Darlan Pase
DP
da Rosa
Luiz Felipe
LF
Forgiarini
Mariel Barbachan
MB
e Silva
Cíntia Zappe
CZ
Fiori
Cristiano Feijó
CF
Andrade
Dênis
D
Martinez
Norma Possa
NP
Marroni
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012891:Sleep Apnea Syndromes / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000975:Antioxidants; 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; D052247:Nitric Oxide Synthase Type II; D020169:Caspases; D008550:Melatonin; D000111:Acetylcysteine