Intermittent Hypoxia and Unsaturated Aldehydes: Effects on Oral Epithelial Wound Healing

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.