COMPARATIVE CYTOTOXICITY EVALUATION OF MEDICINES USED FOR PULPTHERAPY OF PRIMARY TEETH

SUMMARY: Introduction:Despite the eight decades of widespread clinical use of formocresol growing evidence from both experimental and clinical studies clearly indicates that formaldehyde is leaking out during pulpotomy and may participate in the development of non-target tissue damage of local and systemic character. Special attention has been paid to pulp-capping materials and especially mineral trioxide aggregate (MTA) as probable alternative of formocresol in vital pulpotomy in primary teeth, in line with its excellent biocompatibility and pro-dentinogenic properties. The overwhelming evidence that MTA is superior in terms of biological compatibilityand clinical success as compared to formocresol has conditioned the dramatic shift to MTA in routine pulpotomies. Objective: The aim of this study was to assess the biocompatibility of resorcinol/formalin (RF) pulpotomy preparation in comparison to mineral trioxide aggregate (MTA) and calcium hydroxide cement (CHC). Methods: Cell survival was assessed by the MTT- assay (after 48, 72 or 144 h) in five cell lines, namely: HD- MY-Z, HEK-293, SH-SY-5Y, Neuro-2A, SaOS-2. In addition treatment-induced morphological perturbations and induction of necrosis and apoptosis were assessed in HEK-293. Results: RF evoked strong, concentration-dependent cytotoxicity, which was evident even at significant dilution of the parent solution. In general the cytotoxicity of RF was not greatly influenced by the exposure period, especially at the higher concentrations under evaluation. In contrast the MTA extracts proved to be generally devoid of cytotoxic effects. MTA treatment actually increased the viability of SaOS-2 osteosarcoma cells, which could be attributed to the presence of calcium ions in the MTA-eluate which in turn stimulates the proliferation of this cell line.The CH cement extracts showed marginal cytotoxicity which was far less pronounced than that of RF and slightly superior compared to MTA. Conclusions: In contrast to RF that exerted prominent cytotoxicity, MTA and CHC were biocompatible, with no evidence for decreased mitochondrial dehydrogenase activity, morphological changes in monolayer integrity or induction of apoptosis and/or necrosis. This contribution is the first systematic in vitro evaluation of the cytotoxicity of resorcinol- formalin vs. viable pulpotomy agents. It gives further evidence for the safety advantages of viable pulp therapy products CHC and especially MTA as compared to the RF preparation, routinely used in Bulgaria for decades.