# Cytotoxicityicity of Bleaching Products: A Systematic Review
## 4 Materials and Methods
There is evidence that, when comparing different brands, the results in terms of the cytotoxicity produced differ without being a consequence of a higher percentage of one of them [18; 34]. Examples of this are Norblanc and Opalescence, both used at concentrations of 37.5-40% HP, with the latter being more harmful [18]. This is likely due to some additives incorporated in bleaching products, which increase the existing adverse effects. Additionally, it is worth mentioning the common incorporation of thickeners such as carbopol (carboxypolymethylylene polymer), found in most household bleaching products such as carbamide peroxide. Its main function is to slow down the release process, thus extending the reaction time [40; 41]. Whitening can be achieved through various methods. In addition to the application of whitening products in the dental office, there are also home-use products such as whitening toothpastes, aimed at lightening tooth color. These pastes contain abrasive cleaning materials, moisturizers, thickening agents, and fluorides for health benefits. Some whitening pastes also include chemical agents such as HP, sodium citrate, or phosphate salt [42]. Abrasives are insoluble components incorporated into toothpaste to physically remove stains and dental plaque. Significant tooth color changes can be achieved with their use over a certain period and frequency of brushing. Some of these compounds include sodium lauryl sulfate, sodium monofluophosphate, hydrated silica, sodium benzoate, silicon dioxide, calcium carbonate, dicalcium phosphate dihydrate, calcium pyrophosphate, alumina, perlite, and sodium bicarbonate [43]. However, the excessive incorporation of certain abrasives in toothpaste can damage dental structure, despite their necessity in preventing stains. Additionally, studies show differences in cytotoxicity generated depending on the brand name, which is again important depending on the ingredients it contains [30]. This effective cleaning action must be balanced with remineralization at the dental level to ensure the toothpaste formula is adequate and does not damage tooth enamel [44]. To avoid treatment side effects, ongoing research focuses on new formulas, methods, and barriers. Preventive options such as the use of antioxidants are being explored. Vitamin E, for example, is an essential nutrient with various health benefits, including its antioxidant properties. It contains tocopherols and tocotrienols, potent antioxidants capable of eliminating peroxyl radicals [45; 46]. Therefore, studying their interactions with oxidative stress and reactive oxygen species (ROS) is of interest since these are the main mechanisms of action of bleaching. Different concentrations of vitamin E associated with HP application have been evaluated, with evidence of lower cytotoxicity observed at concentrations from 250 uM [14]. Another studied antioxidant compound is N-acetylcysteine, a metabolite of the amino acid cysteine with antioxidant potential. It acts as a bioprotective agent against oxidative stress by eliminating reactive oxygen species [47; 48]. Observations indicate a reduction in HP-associated cytotoxicity with N-acetylcysteine at various concentrations and application times [15]. A recent systematic review indicates how the use of topical otosporin reduces pulpal inflammation when applied after bleaching treatment, as well as the use of remineralizing agents such as bioactive glass-ceramic or MI Paste Plus (a paste made up of casein phosphopeptide and amorphous calcium phosphate) help maintain an alkaline environment, thereby reducing the acidification caused by HP [49]. It is worth noting that the antioxidant potential of such compounds may have a lesser effect on whitening, reducing tooth lightening as they prevent the oxidative reaction involved in treatment. Therefore, their primary recommended use is at a preventive level, as a protector of the gingival barrier, applied to soft tissues to prevent the ROS from damaging periodontal cells.