N-acetyl cysteine prevents pain and hypersensitivity of bleaching agents without affecting their aesthetic appeal; evidence from in vitro to animal studies and to human clinical trials

Abstract Background Tooth hypersensitivity and pain are undesirable side effects of bleaching agents in humans. The aim of this study is to implement strategies to counter such side effects, and to demonstrate the efficacy and mechanisms of action of N-acetyl cysteine (NAC) in countering the side effects of clinically used bleaching agents. Methods In a series of in vitro experiments, animal model studies, and human clinical trials, we demonstrate that NAC protects oral mucosa and teeth from damage induced by bleaching agents. Results The addition of NAC along with clinically used bleaching agents to dental pulp stromal/stem cells (DPSCs), stem-cells of apical papillae (SCAP) and oral epithelial cells, inhibited cell death mediated by bleaching agents in several in vitro assays. In addition, rat teeth, when treated with chair-side or over-the-counter bleaching agents, exerted adverse side effects to pulpal and gingival tissues as evidenced by the white lesions of gingivae as well as decreased survival and function of DPSCs. These side effects of bleaching agents were greatly mitigated by the application of NAC to the surfaces of the teeth and to the oral mucosa. NAC protected the surface topography and the appearance of the tissues after bleaching using scanning electron microscopic (SEM) analysis. Finally, application of NAC prior to the bleaching demonstrated significant translational benefit for the patients since it ameliorated pain and hypersensitivity and protected gingivae from bleaching induced white lesions and improved inflammatory index in the oral mucosa in human clinical trials. Conclusions Therefore, application of NAC to the surfaces of the teeth and oral mucosa prior to the use of bleaching materials is beneficial for countering adverse side effects of bleaching in patients and decreases pain, sensitivity, and potential damage to the dentition and oral mucosa associated with bleaching. Trial registration NCT03534115 (NAC Prevents Side-Effects of Teeth Bleaching). Registration 4 December 2014.