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

这个项目的出发点是我们发现明确的臭氧化氨基酸（主要是半胱氨酸和色氨酸）在口腔细胞中对NF-kappaB系统具有抑制作用，这可以被视为炎症相关信号转导和转录的范例（Huth等人，2007）。申请人因这项发现被授予专利。目前最重要的目标是开发一种高活性抗炎物质，用于治疗炎症过程，如慢性牙周炎。这具有重要的临床意义，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局部免疫反应的活动发生的。这是30-35%的拔牙和52.7%的中度牙周炎患病率（35-44岁）的原因。与先前出版物中显示的工作不同，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成分。将对分离的有效药物进行潜在毒性和诱变特性的检查，并对NF-kappaB激活上游NF-kappaB信号通路中的抑制机制进行表征。最后，在临床炎症过程中，臭氧化氨基酸的活性成分的抗炎效果将在牙周炎小鼠模型中进行测试。

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.