Protein Activation in Periapical Reaction to Iodoform Containing Root Canal Sealer

Objectives: An association between root canal sealers and periapical lesions in primary dentition has been suggested, yet the chemical-protein interactions that may be involved in it have not been studied. The present study explored root sealer components' effect on periapical tissue proteins using bioinformatics tools. Study design: For each chemical component of Endoflas F.S. root sealing material we identified the known and predicted target proteins, using STITCH (search tool for interactions of chemicals http://stitch.embl.de/). Identified target proteins were grouped into functional categories using the annotation clustering tool from DAVID, the Database for Annotation, Visualization and Integrated Discovery (http://david.abcc.ncifcrf.gov/). STRING Protein-Protein Interaction network database identified associations between the proteins. Results: Sixteen proteins identified with STITCH served as input to DAVID annotation clustering tool. Only ZnO and Eugenol targeted proteins had statistically significant annotations. Gene Ontology terms of ZnO and Eugenol targeted proteins demonstrated that these proteins respond to mechanical stimulus and to oxidative stress. They highlight these proteins' role in the positive regulation of transcription, gene expression, cell proliferation and apoptosis, and their complementary role in the negative regulation of cell death. Conclusion: When stimulated by Zinc Oxide, Eugenol and Calcium hydroxide, chemical-protein and subsequent protein-protein interactions result in cell proliferation in the periapical area. Our findings indicate that certain root sealers components may cause enlargement of the permanent tooth follicle. Dentists should be aware of this phenomenon and radiographically monitor root canal treated teeth until shedding.