Abstract
Introduction: Antibiotics are often administered to patients perioperatively and have been shown to affect ROS production of nasal cells in vitro, but their effect in the setting of active wound healing remains unclear. Reactive oxygen species (ROS) are known to play a significant role in wound healing. This study analyzed a broad array of antibiotics used after sinus surgery to assess their effect on wound healing and ROS production in vitro. It was hypothesized that ROS production would be affected by these antibiotics and there would be a negative relationship between ROS activity and cell migration speed.Methods: Monolayers of primary human nasal epithelial cells (HNEC) and primary fibroblasts were disrupted with a linear wound, treated with 10 different antibiotics or a ROS inhibitor and observed over 36 h in a controlled environment using confocal microscopy. ROS activity and migration speed of the wound edge were measured at regular intervals. The relationship between the two parameters was analyzed using mixed linear modeling.Results: Performing a linear scratch over the cell monolayers produced an immediate increase in ROS production of ~35% compared to unscratched controls in both cell types. Incubation with mitoquinone and the oxazolidinone antibiotic linezolid inhibited ROS activity in both fibroblasts and HNEC in association with slowed fibroblast cell migration (p < 0.05). Fibroblast cell migration was also reduced in the presence of clarithromycin and mupirocin (p < 0.05). A significant correlation was seen between ROS suppression and cell migration rate in fibroblasts for mitoquinone and all antibiotics except for azithromycin and doxycycline, where no clear relationship was seen. Treatments that slowed fibroblast cell migration compared to untreated controls showed a significant correlation with ROS suppression (p < 0.05).Conclusion: Increased ROS production in freshly wounded HNEC and fibroblast cell monolayers was suppressed in the presence of antibiotics, in correlation with reduced fibroblast cell migration. In contrast, HNEC cell migration was not significantly affected by any of the antibiotics tested. This differential effect of antibiotics on fibroblast and HNEC migration might have clinical relevance by reducing adhesion formation without affecting epithelial healing in the postoperative setting.
Highlights
Antibiotics are often administered to patients perioperatively and have been shown to affect Reactive oxygen species (ROS) production of nasal cells in vitro, but their effect in the setting of active wound healing remains unclear
We investigate the cytokinetic effect of antibiotics on sinonasal fibroblasts and epithelial cells that have been exposed to mechanical trauma
Performing a linear scratch over the cell monolayers produced an immediate significant increase in ROS production of ∼35% compared to unscratched controls in both cell types (Figures 1A,F,C,H) (p < 0.05)
Summary
Antibiotics are often administered to patients perioperatively and have been shown to affect ROS production of nasal cells in vitro, but their effect in the setting of active wound healing remains unclear. Successful healing involves a complex interplay between many different cell types and the molecular counterparts involved in their cell signaling pathways Where this process becomes dysregulated, bands of scar tissue termed adhesions may form in the nasal cavity between the remnant mucosal structures. This is a dynamic process, whereby surgically traumatized tissues that are in apposition begin to bind together across loose fibrin bridges, formed during the hemostatic stage of wound healing (Watelet et al, 2002). These structures remain highly mobile initially, begin permanently adhering to one another as fibroblasts infiltrate the wound and begin depositing collagen. The process of postoperative adhesion begins during surgery, and the severity and extent of these adhesions may evolve over weeks and months, their incidence is determined within the first postoperative week (Parker, 2004)
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