邻苯烷衍生物可减弱巨噬细胞培养中的TNF-α的产生，并防止实验牙周炎的肺泡骨质损失
Phthalocyanine derivative attenuates TNF-α production in macrophage culture and prevents alveolar bone loss in experimental periodontitis
影响因子:3.40000
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
摘要
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核因子KAPPA B（NF-κB）激活。随后，用牙周炎诱导的韧带局部给予含有1％FETCPC的口腔凝胶对小鼠的牙龈组织施用。在牙龈组织中量化了骨流失和TNFα，p65（NF-κB）和受体激活核因子Kappa B配体（RANKL）的基因表达。最后，在激活的RAW 264.7巨噬细胞培养物中估计了FETCPC的全身毒性，100μMFETCPC降低了TNF-α释放和NF-κB激活。关于实验性牙周炎，含有1％FETCPC的口腔凝胶局部应用阻断肺泡骨质的损失。另外，1％的FETCPC降低了牙龈组织中TNFα，p65（NF-κB）和RANKL的表达。最后，剂量为1至1000 mg/kg的剂量给药不会引起G. mellonella.overall的急性全身毒性。
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.