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改良乳过氧化物酶系统的安全性评估——体外人牙龈成纤维细胞研究。

Safety Assessment of the Modified Lactoperoxidase System-In Vitro Studies on Human Gingival Fibroblasts.

机构信息

Department of Medical Diagnostics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.

Doctoral School of Health and Medical Sciences, Jagiellonian University Medical College, Św. Łazarza 16, 31-008 Kraków, Poland.

出版信息

Int J Mol Sci. 2023 Jan 30;24(3):2640. doi: 10.3390/ijms24032640.

Abstract

One strategy in caries prevention is to inhibit the formation of cariogenic biofilms. Attempts are being made to develop oral hygiene products enriched with various antimicrobial agents. One of them is lactoperoxidase-an enzyme that can oxidise (pseudo)halide ions to reactive products with antimicrobial activity. Currently, commercially available products utilise thiocyanate as a substrate; however, several alternatives that are oxidised to products with greater antimicrobial potential have been found. In this study, toxicity against human gingival fibroblasts of the lactoperoxidase system was evaluated using four different (pseudo)halide substrate systems-thiocyanate, iodide, selenocyanate, and a mixture of thiocyanate and iodide. For this purpose, cells were treated with the systems and then apoptosis, cell cycle, intracellular glutathione concentration, and mitochondrial superoxide production were assessed. The results showed that each system, after generating 250 µM of the product, inhibited cell divisions, increased apoptosis, and increased the percentage of dead cells. It was concluded that the mechanism of the observed phenomena was not related to increased superoxide production or the depletion of glutathione concentration. These findings emphasised the need for the further in vitro and in vivo toxicity investigation of the modified lactoperoxidase system to assess its safety and the possibility of use in oral hygiene products.

摘要

预防龋齿的策略之一是抑制致龋生物膜的形成。目前正在尝试开发含有各种抗菌剂的口腔卫生产品。其中一种是乳过氧化物酶——一种可以将(伪)卤化物离子氧化为具有抗菌活性的反应产物的酶。目前,市售产品使用硫氰酸盐作为底物;然而,已经发现了几种被氧化为具有更大抗菌潜力的产物的替代物。在这项研究中,使用四种不同的(伪)卤化物底物系统——硫氰酸盐、碘化物、硒氰酸盐和硫氰酸盐和碘化物的混合物——评估了乳过氧化物酶系统对人牙龈成纤维细胞的毒性。为此,用这些系统处理细胞,然后评估细胞凋亡、细胞周期、细胞内谷胱甘肽浓度和线粒体超氧化物的产生。结果表明,每个系统在生成 250µM 的产物后,均抑制细胞分裂、增加细胞凋亡并增加死亡细胞的百分比。研究结论表明,观察到的现象的机制与超氧化物产生增加或谷胱甘肽浓度耗竭无关。这些发现强调了需要进一步对改良乳过氧化物酶系统进行体外和体内毒性研究,以评估其安全性及其在口腔卫生产品中的使用可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c73/9916481/f81dfef2fc96/ijms-24-02640-g001.jpg

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