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).
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.
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.
Thus, we show that IH causes liver inflammation and apoptosis, which may be protected with either MEL or NAC.
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- H2O2 :
Hematoxylin and eosin
Hypoxia-inducible factor 1 alpha
- IH + MEL:
Intermittent hypoxia and treatment with melatonin
- IH + NAC:
Intermittent hypoxia and treatment with N-acetylcysteine
Inducible NO synthase
Nuclear factor kappa B
- O •-2 :
Superoxide anion radical
Obstructive sleep apnea syndrome
Simulation of intermittent hypoxia
- SIH + MEL:
Simulation of intermittent hypoxia and treatment with melatonin
- SIH + NAC:
Simulation of intermittent hypoxia and treatment with N-acetylcysteine
Transforming growth factor beta
Tumor necrosis factor
Vascular endothelial growth factor
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Fundo de Investimento à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE-HCPA), Brazil.
Conflict of interest
No conflicts of interest in this work.
Responsible Editor: John Di Battista.
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da Rosa, D.P., Forgiarini, L.F., e Silva, M.B. et al. Antioxidants inhibit the inflammatory and apoptotic processes in an intermittent hypoxia model of sleep apnea. Inflamm. Res. 64, 21–29 (2015). https://doi.org/10.1007/s00011-014-0778-5
- Sleep apnea
- Intermittent hypoxia