## 4 Discussion
### Bleaching with Hydrogen Peroxide  
Hydrogen peroxide (HP) is an active agent widely used during the procedure of external tooth bleaching, both in professional and in at-home-administered products [19; 20]. The mechanism of action of HP is based on complex oxidation that causes the release of active oxygen species and the breakdown of pigments located in enamel and dentin. The active oxygen species formed by HP can permeate through the enamel prisms and reach the dentin, breaking down organic molecules [21]. The smaller and lighter compounds derived from the decomposition of organic molecules are responsible for the reflection of less color resulting in a whitening effect [22]. However, clinical studies reported that HP could reach the pulp chamber, causing adverse side effects. Biochemical changes in the dentin-pulp complex in response to bleaching agents are responsible for TS [23; 24]. In vivo studies demonstrated that HP could cause oxidative stress to human dental pulp cells, interfering with odontoblastic differentiation. The presence of peroxides and their subproducts could activate the TRPA1 channel (transient receptor potential cation channel with anxyrin domain-type), which is associated with pain. In the same study, the authors demonstrated that the ozone therapy associated with HP does not interfere with bleaching and can reduce the side effects [21]. A study by [PERSON] et al. revealed that remineralizing pastes, based on casein phospho-peptide-amorphous calcium phosphate (CPP-ACP), in association with 35% HP bleaching gel, could promote a significant reduction of pulp inflammation after bleaching [25]. Direct contact with HP could induce genotoxic effects on oral mucosa cells and gingival irritation [26]. In vivo, studies showed an increase of cytotoxic biomarkers in saliva, directly related to nuclear and oxidative DNA damage of oral mucosa cells directly exposed to HP-based products. These data suggest that caustic side effects could be due to a cellular protective mechanism of gingival and lip mucosa cells [27]. Changes in the enamel micro-hardness and increasing surface roughness because of bleaching products are effects reported in the literature [28]. The diffusion of HP on the hard tissue could depend on the concentration and contact time [29]. Many alternative methods in conjunction with HP products have been proposed to increase the biocompatibility of bleaching therapy. Several bleaching systems, application protocols, contact time, and different concentrations of HP gels were compared to detect the efficacy in terms of color and the risk of TS. A clinical trial on 78 patients, carried out by [PERSON] et al., revealed that 10% HP increased the intensity of TS rather than 4% HP concentrations during at-home bleaching [23]. The risk of TS appears higher for 35% HP than for 15% HP after in-office bleaching treatment, according to the study by [PERSON] et al. [30]. A study by [PERSON] et al. showed that 30 min/day of 4% HP trays at-home application whitened teeth similarly to the recommended 120 min/day application time and significantly reduced TS [31]. In-office bleaching performed by 38% HP gel applied under different time protocols did not show differences in terms of efficacy whether the bleaching agent was used in a 40-min application or two 20-min applications, according to the results by [PERSON] et al. [29]. Based on the study by [PERSON] et al., a strip system of 2.9% HP was significantly more effective than the paint-on-type during at-home treatment [26]. At-home dental bleaching performed with 10% HP gel applied on the lingual surfaces seemed to promote worse results in bleaching efficacy rather than the application of gel on buccal surfaces [19]. A clinical trial on twenty-eight patients was carried out to assess the 1-year color stability produced by the different pH of HP gels when used as in-office treatments. No significant differences were obtained between the applications of neutral and acid gels [32].