The effect of ozonised amino acids and their isolated active components on inflammation-associated signal transduction and in a model of periodontitis, together with analysis of mutagenesis

臭氧化氨基酸及其分离的活性成分对炎症相关信号转导和牙周炎模型的影响，以及诱变分析

• 批准号: 234417066
• 负责人: Professorin Dr. Karin Christine Huth
• 金额: --
• 依托单位: Poliklinik für Zahnerhaltung und Parodontologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/234417066?language=en
• 关键词: effect; ozonised; amino; acids; their

The starting point for this proposed project was our discovery that defined, ozonised amino acids (primarily cysteine and trytophan) show an inhibitory effect, in oral cells, on the NF-kappaB system, which can be seen as a paradigm for inflammation-associated signal transduction and transcription (Huth et al., 2007). The applicant was awarded a patent for this discovery. The overriding goal is now the development of a highly active anti-inflammatory substance to be used in the treatment of inflammatory processes, such as chronic periodontitis. This has great clinical relevance, since, despite the fact that periodontitis is caused by periodontal pathogenic bacteria, the actual tissue damage occurs through the activity of the local immune response in a chronic inflammatory process. This is the cause of 30-35% of tooth extractions and a prevalence of moderate periodontitis of 52.7% (35-44 year olds). Distinct from the work shown in the previous publication, it is now necessary to isolate and identify the actual active components found in the reaction mix formed following ozonisation of the amino acids. The isolated effective agents will be examined with respect to potential toxic and mutagenic properties and their inhibitory mechanism in the NF-kappaB signalling pathway upstream of NF-kappaB activation will be characterised. Finally, the anti-inflammatory effectiveness of the active components of the ozonised amino acids within a clinical inflammatory process will be tested in a mouse model of periodontitis.

该提议项目的起点是我们发现，确定的臭氧化氨基酸（主要是半胱氨酸和色氨酸）在口腔细胞中对NF-κ B系统显示出抑制作用，这可以被视为炎症相关信号转导和转录的范例（Huth et al.，2007年）。申请人因这一发现获得了专利。目前最重要的目标是开发一种高活性的抗炎物质，用于治疗炎症过程，如慢性牙周炎。这具有很大的临床意义，因为尽管牙周炎是由牙周致病菌引起的，但实际的组织损伤是通过慢性炎症过程中的局部免疫应答的活性发生的。这是30-35%的拔牙和52.7%的中度牙周炎患病率（35-44奥尔兹）的原因。与先前出版物中所示的工作不同，现在有必要分离和鉴定在氨基酸臭氧化后形成的反应混合物中发现的实际活性组分。将检查分离的有效药物的潜在毒性和致突变性，并表征其在NF-κ B活化上游NF-κ B信号传导途径中的抑制机制。最后，将在牙周炎的小鼠模型中测试臭氧化氨基酸的活性组分在临床炎症过程中的抗炎效果。