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Antioxidants inhibit the inflammatory and apoptotic processes in an intermittent hypoxia model of sleep apnea

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Abstract

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.

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Abbreviations

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CAT:

Catalase

EDTA:

Ethylenediaminetetraacetic acid

H2O2 :

Hydrogen peroxide

HE:

Hematoxylin and eosin

HEPES:

(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid)

HIF-1α:

Hypoxia-inducible factor 1 alpha

IH:

Intermittent hypoxia

IH + MEL:

Intermittent hypoxia and treatment with melatonin

IH + NAC:

Intermittent hypoxia and treatment with N-acetylcysteine

iNOS:

Inducible NO synthase

KCl:

Potassium chloride

MEL:

Melatonin

NAC:

N-Acetylcysteine

NaCl:

Sodium chloride

NASH:

Nonalcoholic steatohepatitis

NF-kB:

Nuclear factor kappa B

NO:

Nitric oxide

O •-2 :

Superoxide anion radical

OSA:

Obstructive sleep apnea syndrome

PVDF:

Polyvinylidene difluoride

SIH:

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

SOD:

Superoxide dismutase

TGF-β:

Transforming growth factor beta

TNF-alpha:

Tumor necrosis factor

VEGF:

Vascular endothelial growth factor

XO:

Xanthine oxidase

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Acknowledgments

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.

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Authors and Affiliations

  1. Programa de Pós-Graduação Medicina, Ciências Médicas, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, CEP 90670-001, Brazil

    Darlan Pase da Rosa, Cíntia Zappe Fiori, Dênis Martinez & Norma Possa Marroni

  2. Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, CEP 90035-903, Brazil

    Darlan Pase da Rosa, Luiz Felipe Forgiarini, Cíntia Zappe Fiori, Cristiano Feijó Andrade, Dênis Martinez & Norma Possa Marroni

  3. Faculdade Cenecista de Bento Gonçalves, Porto Alegre, RS, CEP 90670-001, Brazil

    Darlan Pase da Rosa

  4. Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, CEP 90035-903, Brazil

    Luiz Felipe Forgiarini & Cristiano Feijó Andrade

  5. Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, CEP 90035-903, Brazil

    Mariel Barbachan e Silva

  6. Universidade Luterana do Brasil, Porto Alegre, RS, CEP 90035-903, Brazil

    Norma Possa Marroni

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  1. Darlan Pase da Rosa
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Correspondence to Darlan Pase da Rosa.

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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

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