Abstract
Obstructive sleep apnea (OSA) is a highly prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), leading to blood hypoxemia, hypercapnia, and sleep fragmentation. Studies on the effects of OSA on oral epithelial tissue healing are limited. Smoking is considered a risk factor for OSA through the exposure to chemically active toxins, present in the smoke. Acrolein is the most chemically active unsaturated aldehyde, impairing a variety of biological processes. The aim of this study was to determine the effect of IH on oral epithelial tissue healing, with and without acrolein. HaCaT cells were wounded by a cross-scratch made in the cell cultures, considered as time zero. Then, cells were exposed to 28 IH cycles (5–20% oxygen) during 12 h using the BioSpherix OxyCycler-C42 system. Control cells were maintained in normoxic conditions or in sustained hypoxia (SH) (5% oxygen) for the same durations, after which all cells were maintained for additional 12 h in normoxia. The migrating abilities of cells were measured after 24 h by calculating the percent of the residual cross-scratch area. In parallel experiments, 25 μM acrolein were added to each treatment. We found that the scratch closure was the slowest under IH. After 24 h, the residual scratch area in the IH treated cells was 29.5 ± 13.4% of the initial area, while in normoxia and SH it was 9.2 ± 5.8% and 10.3 ± 11.3%, respectively (p < 0.01 for both vs. IH). Adding acrolein further attenuated the migratory ability in IH as compared to normoxia and SH. We conclude that IH delays the healing process of oral epithelial tissue by slowing the cells’ migratory abilities. The healing might be further attenuated by chemically active unsaturated aldehydes such as acrolein.
References
Almendros I, Montserrat JM, Torres M, Bonsignore MR, Chimenti L, Navajas D, Farré R (2012) Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep apnea. Sleep Med 13(10):1254–1260
Avezov K, Reznick AZ, Aizenbud D (2014) Oxidative damage in keratinocytes exposed to cigarette smoke and aldehydes. Toxicol In Vitro 28(4):485–491
Berger S, Aronson D, Lavie P, Lavie L (2013) Endothelial progenitor cells in acute myocardial infarction and sleep-disordered breathing. Am J Respir Crit Care Med 187(1):90–98
Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston-Martin S, Bernstein L, Schoenberg JB, Stemhagen A, Fraumeni JF Jr (1988) Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 48(11):3282–3287
Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE (1998) Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 106(3):761–771
Briançon-Marjollet A, Henri M, Pépin J-L, Lemarié E, Lévy P, Tamisier R (2014) Altered in vitro endothelial repair and monocyte migration in obstructive sleep apnea: implication of VEGF and CRP. Sleep 37(11):1825–1832
Cikutovic M, Fuentes N, Bustos-Obregón E (2009) Effect of intermittent hypoxia on the reproduction of rats exposed to high altitude in the Chilean Altiplano. High Alt Med Biol 10(4):357–363
Dyugovskaya L, Lavie P, Lavie L (2002) Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med 165(7):934–993
Dyugovskaya L, Polyakov A, Lavie P, Lavie L (2008) Delayed neutrophil apoptosis in patients with sleep apnea. Am J Respir Crit Care Med 177(5):544–554
Ge Y, Xu Y, Sun W, Man Z, Zhu L, Xia X, Zhao L, Zhao Y, Wang X (2012) The molecular mechanisms of the effect of dexamethasone and Cyclosporin A on TLR4/NF-κB signaling pathway activation in oral lichen planus. Gene 508(2):157–164
Grimsrud PA, Xie H, Griffin TJ, Bernlohr DA (2008) Oxidative stress and covalent modification of protein with bioactive aldehydes. J Biol Chem 283(32):21837–21841
Gunaratnam K, Taylor B, Curtis B, Cistulli P (2009) Obstructive sleep apnoea and periodontitis: a novel association? Sleep Breath 13(3):233–239
Johnson GK, Guthmiller JM (2007) The impact of cigarette smoking on periodontal disease and treatment. Periodontol 44(1):178–194
Kashyap R, Hock LM, Bowman TJ (2001) Higher prevalence of smoking in patients diagnosed as having obstructive sleep apnea. Sleep Breath 5(4):167–172
Lavie L (2003) Obstructive sleep apnoea syndrome-an oxidative stress disorder. Sleep Med Rev 7(1):35–51
Lavie L (2015) Oxidative stress in obstructive sleep apnea and intermittent hypoxia-revisited-the bad ugly and good: implications to the heart and brain. Sleep Med Rev 20:27–45
Lavie L, Lavie P (2008) Smoking interacts with sleep apnea to increase cardiovascular risk. Sleep Med 9(3):247–253
Lavie L, Lavie P (2009) Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link. Eur Respir 33(6):1467–1484
Lévy P, Kohler M, McNicholas WT, Barbé F, McEvoy RD, Somers VK, Lavie L, Pépin JL (2015) Obstructive sleep apnoea syndrome. Nat Rev Dis Prim 1:15015. doi:10.1038/nrdp.2015.15
Nagler R, Lischinsky S, Diamond E, Drigues N, Klein I, Reznick AZ (2000) Effect of cigarette smoke on salivary proteins and enzyme activities. Arch Biochem Biophys 379(2):229–236
Nieto FJ, Peppard PE, Young T, Finn L, Hla KM, Farré R (2012) Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study. Am J Respir Crit Care Med 186(2):190–194
O’Neill CA, Halliwell B, van der Vliet A, Davis PA, Packer L, Tritschler H, Strohman WJ, Rieland T, Cross CE, Reznick AZ (1994) Aldehyde-induced protein modifications in human plasma: protection by glutathione and dihydrolipoic acid. J Lab Clin Med 124(3):359–370
Payne RJ, Hier MP, Kost KM, Black MJ, Zeitouni AG, Frenkiel S, Naor N, Kimoff RJ (2005) High prevalence of obstructive sleep apnea among patients with head and neck cancer. J Otolaryngol 34(5):304–311
Reibel J (2003) Tobacco and oral diseases. Update on the evidence, with recommendations. Med Princ Pract 12(Suppl 1):22–32
Reinke C, Bevans-Fonti S, Grigoryev DN, Drager LF, Myers AC, Wise RA, Schwartz AR, Mitzner W, Polotsky VY (2011) Chronic intermittent hypoxia induces lung growth in adult mice. Am J Physiol Lung Cell Mol Physiol 300(2):L266–L273
Swan GE, Lessov-Schlaggar CN (2007) The effects of tobacco smoke and nicotine on cognition and the brain. Neuropsychol Rev 17(3):259–273
Yang C, Ling H, Zhang M, Yang Z, Wang X, Zeng F, Wang C, Feng J (2011) Oxidative stress mediates chemical hypoxia-induced injury and inflammation by activating NF-κb-COX-2 pathway in HaCaT cells. Mol Cells 31(6):531–538
Conflicts of Interest
The authors declared no competing interests in relation to this article.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Avezov, K., Lavie, L., Aizenbud, D. (2017). Intermittent Hypoxia and Unsaturated Aldehydes: Effects on Oral Epithelial Wound Healing. In: Pokorski, M. (eds) Pulmonary Disorders and Therapy. Advances in Experimental Medicine and Biology(), vol 1023. Springer, Cham. https://doi.org/10.1007/5584_2017_68
Download citation
DOI: https://doi.org/10.1007/5584_2017_68
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-73702-7
Online ISBN: 978-3-319-73703-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)