Mouth gel containing phthalocyanine derivative attenuates TNF-α through NF-κB inhibition in experimental periodontitis

Isadora Breseghello, Rafaela Franco Dias Bruzadelli, Pedro Luiz Rosalen, Leonardo Pereira Araújo, Henrique Ballassini Abdalla, Josy Goldoni Lazarini, Isadora Marques Paiva, Bruno Bueno-Silva, Severino Matias Alencar, Fabiano Vieira Vilhena, Thiago Mattar Cunha, Masaharu Ikegaki, Leandro Araújo Fernandes, Marcelo Franchin
2024 · doi:10.21203/rs.3.rs-4181301/v1
preprint OA: closed CC-BY-4.0
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Abstract

Background: Tumor necrosis factor alpha (TNF-α) is a major cytokine involved in periodontal disease pathogenesis due to its ability to modulate inflammatory cytokine production and cell influx in tooth-supporting tissues. Therefore, TNF-α is an excellent target for limiting the inflammatory process and avoiding alveolar bone resorption and tooth loss. Objective This study investigated the activity and action mechanism behind the anionic iron phthalocyanine (AI-PhyC) derivative on TNF-α production and the impact on experimental periodontitis. Methods RAW 264.7 macrophages were treated with AI-PhyC, and cell viability (MTT) was assessed. Afterward, cells were treated with AI-PhyC, primed with LPS (10ng/mL), and the TNF-α levels were measured, as well as the NF-kB activation and the gene expression of Ikkβ . Subsequently, a mouth gel containing 1% AI-PhyC was topically administered in the gingival tissue of mice with periodontitis ligature-induced. Bone loss and the gene expression of Tnfα , Ikkβ , p65 (NF-κB), and receptor-activating nuclear factor kappa B ligand ( Rankl ) were quantified in the gingival tissue. Lastly, the systemic toxicity of AI-PhyC was estimated in Galleria mellonella larvae. Results In an activated RAW 264.7 macrophage cell culture, AI-PhyC at 100µM reduced TNF-α release, nuclear factor kappa B (NF-kB) activation and mRNA expression of Ikkβ . Regarding the experimental periodontitis, topical application of mouth gel containing 1% AI-PhyC blockage alveolar bone loss. Additionally, 1% AI-PhyC reduced the mRNA expression of Tnfα , Ikkβ , p65 (NF-κB), and Rankl in the gingival tissue. Finally, administering AI-PhyC ranging from 1 to 1000mg/kg did not present acute systemic toxicity (72h) in G. mellonella . Conclusion Overall, we demonstrate the potential of mouth gel containing AI-PhyC as a therapeutic strategy for managing osteolytic inflammatory disorders, such as periodontitis.

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License: CC-BY-4.0