期刊
SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-020-78134-3
关键词
-
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC Grant) [RGPIN-2018-06919, RGPIN-2019-07076]
- Fondation Courtois (Quebec, Canada) from the Ministere des Relations Internationales et de la Francophonie (MRIF, Quebec, Canada)
- Ministry of Foreign Affairs and International Cooperation (Italy)
- Fonds de la Recherche du Quebec-Sante (Quebec, Canada)
- CRIPA/FRQNT
- Fonds de la Recherche du Quebec-Sante
Excess of histamine in gut lumen generates a pronounced gastrointestinal discomfort, which may include diarrhea and peristalsis dysfunctions. Deleterious effects of histamine can be alleviated with antihistamine drugs targeting histamine receptors. However, many antihistamine agents come with various undesirable side effects. Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. Mammalian intestinal mucosa contains an endogenous DAO, yet possessing lower activity compared to that of vDAO preparation. Moreover, in several pathological conditions such as inflammatory bowel disease and irritable bowel syndrome, this endogenous DAO enzyme can be lost or inactivated. Here, we tested the therapeutic potential of vDAO by focusing on the well-known effect of histamine on gut motility. Using ex vivo and in vitro assays, we found that vDAO is more potent than commercial anti-histamine drugs at inhibiting histamine-induced contraction of murine distal colon muscles. We also identified pyridoxal 5 ' -phosphate (the biologically active form of vitamin B6) as an effective enhancer of vDAO antispasmodic activity. Furthermore, we discovered that rectally administered vDAO can be retained on gut mucosa and remain active. These observations make administration of vDAO in the gut lumen a valid alternative treatment for histamine-induced intestinal dysfunctions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据