The Effect of Intermittent Hypoxia and Unsaturated Aldehydes on Epithelial Wound Healing

Objectives: Obstructive sleep apnea (OSA) is a highly prevalent breathing disorder in sleep characterized by intermittent hypoxia (IH) leading to blood hypoxemia, hypercapnia and sleep fragmentation. OSA is associated with numerous systemic disorders. However, studies on its effect on oral tissues are limited and the effects of IH on epithelial tissue healing are inconclusive. A considerable number of OSA patients are smokers, whose oral tissues are constantly subjected to chemically active toxins, including unsaturated aldehydes. Acrolein is the most chemically active aldehyde, since its double bond is capable of inactivating a wide range of macromolecules and interfering with a variety of biological processes. The objectives of the current study were to examine the effects of IH on epithelial tissue healing processes, with and without acrolein.
Methods: The keratinocyte HaCaT cell line was chosen to represent oral-keratinocytes. The cells were exposed to 36 IH cycles during 12 hours using the BioSpherix OxyCycler C42 system. In parallel, control cells were maintained in normoxic conditions or in sustained hypoxia (SH) for the same duration. A cross scratch was made in the cell cultures at time-0 and the migrating abilities of cells were measured after 24 hours, by calculating the percent of the residual cross scratch area. In parallel experiments, 25 μM acrolein was added to each treatment.
Results: The scratch closure was the slowest under IH. After 24 hours 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. Adding acrolein further attenuated the migratory ability in IH by about 50%.
Conclusions: IH may cause a delay in the healing process of epithelial tissues by slowing their migratory abilities. Chemically active unsaturated aldehydes such as acrolein may further slow the healing of epithelial tissues under IH.