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用于牙髓病治疗的抗生素和基于表没食子儿茶素的药物的抗生物膜特性、细胞毒性及对蛋白酶活性的影响。

Antibiofilm properties, cytotoxicity, and effect on protease activity of antibiotics and EGCG-based medications for endodontic purposes.

作者信息

Chrisostomo Daniela Alvim, Pereira Jesse Augusto, Scaffa Polliana Mendes Candia, Gouveia Zach, Abuna Gabriel Flores, Plotnikov Sergey V, Prakki Anuradha, Duque Cristiane

机构信息

São Paulo State University (UNESP), Department of Preventive and Restorative Dentistry, School of Dentistry, Araçatuba, SP, Brazil; University of Toronto, Department of Clinical Sciences, Faculty of Dentistry, Toronto, ON, Canada.

São Paulo State University (UNESP), Department of Preventive and Restorative Dentistry, School of Dentistry, Araçatuba, SP, Brazil.

出版信息

J Dent. 2025 May;156:105660. doi: 10.1016/j.jdent.2025.105660. Epub 2025 Mar 2.

DOI:10.1016/j.jdent.2025.105660
PMID:40037465
Abstract

OBJECTIVE

To evaluate the effect of two intracanal medications (IM) containing epigallocatechin-3-gallate (EGCG) with fosfomycin (FOSFO) and a triantibiotic combination of metronidazole, ciprofloxacin and fosfomycin (TRI), compared to controls calcium hydroxide (CH), all dissolved in polyethylene glycol 400 (PEG) on multispecies biofilms, fibroblast toxicity and on collagenolytic and gelatinolytic activities detected in radicular dentin.

METHODS

The antibiofilm effect and cytotoxicity of medications containing EGCG + FOSFO, TRI or CH were evaluated on multispecies biofilms formed in bovine root dentin specimens by confocal microscopy and on fibroblasts by resazurin assays, respectively. The inhibition of protease activity of each IM was evaluated by measuring collagenolytic enzyme activity by ELISA (Enzyme-linked immunosorbent assay) and gelatinolytic activity by metalloproteinases (MMPs) using in situ zymography in radicular dentin specimens.

RESULTS

PEG containing EGCG+FOSFO, PEG+TRI, and PEG+CH significantly reduced multispecies biofilms in radicular dentin tubules. At the concentrations tested, those IM were not toxic to fibroblasts. Additionally, all IM presented anti-collagenolytic activity by reducing telopeptide fragments released from radicular dentin compared to PEG carrier and water controls. In situ gelatinolytic activity, assessed via fluorescence levels, was significantly lower in radicular dentin adjacent to PEG containing CH, EGCG+FOSFO, or TRI compared to PEG and water controls.

CONCLUSION

EGCG+FOSFO and TRI in PEG-400 exhibited antibiofilm, anti-collagenolytic and anti-gelatinolytic properties at concentrations that were non-toxic to fibroblasts, making them feasible intracanal medications for endodontic applications.

CLINICAL SIGNIFICANCE

EGCG-based medications enhance the efficacy of endodontic treatment by providing antibiofilm, anti-collagenolytic, and anti-gelatinolytic properties, contributing to the preservation of root structure and improved treatment outcomes.

摘要

目的

评估两种含表没食子儿茶素-3-没食子酸酯(EGCG)与磷霉素(FOSFO)的根管内用药(IM)以及甲硝唑、环丙沙星和磷霉素的三联抗生素组合(TRI),与对照氢氧化钙(CH)相比,在多菌种生物膜、成纤维细胞毒性以及在根管牙本质中检测到的胶原olytic和明胶olytic活性方面的效果,所有药物均溶解于聚乙二醇400(PEG)中。

方法

分别通过共聚焦显微镜评估含EGCG + FOSFO、TRI或CH的药物对牛牙根牙本质标本中形成的多菌种生物膜的抗生物膜作用,以及通过刃天青试验评估对成纤维细胞的细胞毒性。通过酶联免疫吸附测定(ELISA)测量胶原olytic酶活性以及使用根管牙本质标本中的原位酶谱法通过金属蛋白酶(MMPs)测量明胶olytic活性,来评估每种IM的蛋白酶活性抑制情况。

结果

含EGCG+FOSFO的PEG、PEG+TRI和PEG+CH显著减少了根管牙本质小管中的多菌种生物膜。在所测试的浓度下,那些IM对成纤维细胞无毒。此外,与PEG载体和水对照相比,所有IM通过减少从根管牙本质释放的端肽片段而呈现抗胶原olytic活性。通过荧光水平评估的原位明胶olytic活性,与PEG和水对照相比,在含CH、EGCG+FOSFO或TRI的PEG相邻的根管牙本质中显著更低。

结论

PEG - 400中的EGCG+FOSFO和TRI在对成纤维细胞无毒的浓度下表现出抗生物膜、抗胶原olytic和抗明胶olytic特性,使其成为牙髓病应用中可行的根管内用药。

临床意义

基于EGCG的药物通过提供抗生物膜、抗胶原olytic和抗明胶olytic特性增强牙髓病治疗的疗效,有助于保存牙根结构并改善治疗结果。

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