The Hormetic Effect of Arsenic Trioxide on Rat Pulpal Cells: An In Vitro Preliminary Study.

Abstract

Objectives Despite the agreement that there is no longer any indication for arsenic use in modern endodontics, some concerns are surfacing about the minute amount of arsenic trioxide (As 2 O 3 ) released from Portland cement-based materials. The present study investigated the effect of different concentrations of As 2 O 3 on rat pulpal cells and the efficacy of N -acetylcysteine (NAC) in preventing As 2 O 3 -mediated toxicity. Materials and Methods Cytotoxicities of 50, 10, or 5 µm As 2 O 3 and the effect of cells co-treatment with 50 µm As 2 O 3 and 5,000 µm NAC or 500 µm NAC were tested at 24 hours or 3 days. Cell viability was assessed by means of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and cellular morphological changes were observed under phase contrast microscope. Statistical Analysis Two-way analysis of variance with Tukey’s post-hoc test was used to evaluate differences between the groups (α = 0.05). Results At both exposure times, 50 µm As 2 O 3 resulted in lower optical density (OD) values when compared with 10 or 5 µm As 2 O 3 . At 24 hours, 10 µm As 2 O 3 resulted in a higher OD value compared with the control; however, at 3 days the difference was statistically insignificant. At each exposure time, the OD value of 5 µm As 2 O 3 group was comparable to the control and 10 µm As 2 O 3 group. There were no significant differences between 50 µm As 2 O 3 group and 500 μm NAC+50 μm As 2 O 3 group; however, these two groups had lower OD values when compared with 5,000 μm NAC+50 μm As 2 O 3 group at 24 hours and 3 days. The latter group showed significantly lower OD value in comparison with the control at 24 hours and 3 days. Control cells were polygonal-shaped while 50 µm As 2 O 3 -treated cells exhibited contracted and spherical morphology with increased intercellular spaces. At 24 hours, 10 μm and 5 µm As 2 O 3 -treated cells were slightly hypertrophic. Cells co-treated with NAC and As 2 O 3 showed increased intercellular spaces and lower cellular density compared with the control. Conclusions As 2 O 3 displayed a hormetic effect on pulpal cells; however, the proliferative effect induced by low As 2 O 3 concentrations should be interpreted with caution. NAC did not prevent As 2 O 3 -mediated toxicity; however, it demonstrated potential for ameliorating this toxicity.