Antimicrobial activity of NO-releasing compounds against periodontal pathogens

Abstract

This study describes the successful synthesis of nitric oxide (NO)-releasing compounds with biodegradable and injectable properties and demonstrates that the kinetics of NO release vary according to the type of NO donor. The antimicrobial activity of NO-releasing compounds against three common periodontal pathogens, i.e., Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Actinomyces israelii, was investigated using a susceptibility assay. Human gingival fibroblasts were treated with NO-releasing compounds at the minimum concentrations required for bacterial growth and cytotoxicity was evaluated using the MTT cell proliferation assay. Our results suggest that NO-releasing compounds can be used topically to treat both gram-negative and gram-positive periodontal pathogens. Comparison of the antimicrobial activity and cytotoxicity assay results between the NO-releasing compounds revealed that an NO donor comprising a macromolecule without surface charge, a lower instantaneous NO concentration, and an adequate supply of NO were associated with a strong bactericidal effect and low cytotoxicity. NO-releasing compounds with these properties may be suitable for treatment of periodontitis.

Nitric Oxide Donor Modulates a Multispecies Oral Bacterial Community—An In Vitro Study

“…It has been reported that interdental plaques contain relatively large amounts of F. nucleatum [58], and in fact, significant reductions of the three subspecies of F. nucleatum could be confirmed. However, although the bactericidal effect of NO against Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans has previously been reported [30,32], statistical analysis in this study failed to show vulnerability against this NO toxicity. The major cause is that the OTUs corresponding to these bacteria were hardly detectable in the samples, since interdental plaques from young subjects with healthy periodontal tissues were used.…”

“…It has been reported that approximately 0.1 μM NO was detected in collected dental plaque [29]. NO had antimicrobial activity against some oral bacteria such as Porphyromonas gingivalis , Aggregatibacter actinomycetemcomitans , and Actinomyces israelii [30,31,32]. In addition, there seem to be some differences in NO sensitivity among oral bacterial species [30,31].…”

“…To date, although the bactericidal effect of NO on several oral bacteria has been investigated [30,31,32], how the bacterial microbiota structure shifts due to NO generated internally in the oral cavity or NO added from the outside has not yet been clarified. The purpose of this study was to investigate the effect of NO on the overall structure of a multispecies oral bacterial community and to obtain empirical data for controlling the community structure using nitrate and exogenous NO.…”

Nitric Oxide in Dental Pulp Tissue: From Molecular Understanding to Clinical Application in Regenerative Endodontic Procedures

“…46 In addition, recent studies reported that exogenous NO from a NO-releasing compound, such as pluronic F68-branched polyethylenimine-NONOates (F68-BPEI-NO) and NO-releasing silica nanoparticles, showed an adequate antimicrobial effect against specific periodontal pathogens with minimal cytotoxicity to human gingival fibroblasts. 108,150 In contrast to NO donors, synthetic NO scavengers, such as 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) and 2phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIOs), can directly counteract NO through direct radical/radical coupling interactions with NO and may play beneficial roles in therapeutic strategies for oxidative stress-related diseases. 29 A recent study reported that PTIOs can negatively regulate the odontoblast differentiation of rat DPCs induced by the NO donor NOC-18.…”

Recent Advances in Injectable Hydrogels for Biomedical Applications

“…More recently, block copolymer based injectable hydrogels have been explored for periodontitis. Methoxy polyethylene glycol-(polycaprolactone) [26] and F127 [27] block copolymer have been reported as biofriendly materials. Looking at several examples presented above, we believe that injectable hydrogels have their own future.…”