酞蓝素衍生物抑制巨噬细胞培养中TNF-α的生成并预防实验性牙周炎中的牙槽骨丧失

Phthalocyanine derivative attenuates TNF-α production in macrophage culture and prevents alveolar bone loss in experimental periodontitis

JOURNAL OF PERIODONTAL RESEARCH

影响因子:3.4

分区:医学3区 / 牙科与口腔外科3区

发表日期:2025 Apr

作者: Isadora Breseghello, Pedro Luiz Rosalen, Rafaela Franco Dias Bruzadelli, Leonardo Pereira de Araújo, Henrique Ballassini Abdalla, Josy Goldoni Lazarini, Isadora Marques Paiva, Bruno Bueno-Silva, Márcia Regina Cordeiro, Severino Matias de Alencar, Fabiano Vieira Vilhena, Thiago Mattar Cunha, Leandro Araújo Fernandes, Masaharu Ikegaki, Marcelo Franchin

DOI: 10.1111/jre.13341

摘要

本研究探讨了铁四羧酞蓝素（FeTcPc）对肿瘤坏死因子α（TNF-α）产生的作用机制及其在实验性牙周炎中的影响。将RAW 264.7巨噬细胞在100 μM FeTcPc作用下，用10 ng/mL脂多糖（LPS）激活，测定TNF-α水平和核因子κB（NF-κB）活性。随后，将含1% FeTcPc的口腔凝胶局部应用于动物模型的牙龈组织中，检测牙槽骨丧失情况及Tnfα、p65（NF-κB）和受体激活核因子κB配体（Rankl）的基因表达。最后，在Galleria mellonella幼虫中评估FeTcPc的系统毒性。在激活的RAW 264.7巨噬细胞中，100 μM FeTcPc显著降低TNF-α的释放和NF-κB的活性。就实验性牙周炎模型而言，含1% FeTcPc的口腔凝胶局部应用阻断了牙槽骨的吸收。此外，1%的FeTcPc还显著降低了牙龈组织中的Tnfα、p65（NF-κB）及Rankl的表达。在G. mellonella中，剂量范围为1到1000 mg/kg的FeTcPc未引起急性系统毒性。综上所述，我们验证了含FeTcPc的口腔凝胶作为治疗骨溶解性炎症性疾病（如牙周炎）的潜在策略。

Abstract

This study investigated the activity and mechanism of action of the iron tetracarboxyphthalocyanine (FeTcPc) on tumor necrosis factor alpha (TNF-α) production and its impact on experimental periodontitis.RAW 264.7 macrophages were treated with FeTcPc, activated with lipopolysaccharide (LPS) at 10 ng/mL, and the TNF-α levels were measured, as well as the nuclear factor kappa B (NF-κB) activation. Subsequently, a mouth gel containing 1% FeTcPc was topically administered to the gingival tissue of mice with periodontitis-induced ligatures. Bone loss and the gene expression of Tnfα, p65 (NF-κB), and receptor-activating nuclear factor kappa B ligand (Rankl) were quantified in gingival tissue. Finally, the systemic toxicity of FeTcPc was estimated in Galleria mellonella larvae.In an activated RAW 264.7 macrophage culture, 100 μM FeTcPc reduced TNF-α release and NF-κB activation. Regarding experimental periodontitis, topical application of mouth gel containing 1% FeTcPc blocked alveolar bone loss. Additionally, 1% FeTcPc reduced the expression of Tnfα, p65 (NF-κB), and Rankl in gingival tissue. Finally, administration FeTcPc at doses ranging from 1 to 1000 mg/kg did not cause acute systemic toxicity in G. mellonella.Overall, we demonstrated the potential of mouth gel containing FeTcPc as a therapeutic strategy for managing osteolytic inflammatory disorders, such as periodontitis.