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- Title
Combined Administration of Pravastatin and Metformin Attenuates Acute Radiation-Induced Intestinal Injury in Mouse and Minipig Models.
- Authors
Kim, Jung Moon; Kim, Hyewon; Oh, Su Hyun; Jang, Won Il; Lee, Seung Bum; Park, Mineon; Kim, Soyeon; Park, Sunhoo; Shim, Sehwan; Jang, Hyosun
- Abstract
Radiation-induced gastrointestinal (GI) damage is one of the critical factors that serve as basis for the lethality of nuclear accidents or terrorism. Further, there are no Food and Drug Administration-approved agents available to mitigate radiation-induced intestinal injury. Although pravastatin (PS) has been shown to exhibit anti-inflammatory and epithelial reconstructive effects following radiation exposure using mouse and minipig models, the treatment failed to improve the survival rate of high-dose irradiated intestinal injury. Moreover, we previously found that metformin (MF), a common drug used for treating type 2 diabetes mellitus, has a mitigating effect on radiation-induced enteropathy by promoting stem cell properties. In this study, we investigated whether the combined administration of PS and MF could achieve therapeutic effects on acute radiation-induced intestinal injury in mouse and minipig models. We found that the combined treatment markedly increased the survival rate and attenuated histological damage in a radiation-induced intestinal injury mouse model, in addition to epithelial barrier recovery, anti-inflammatory effects, and improved epithelial proliferation with stem cell properties. Furthermore, in minipig models, combined treatment with PS and MF ameliorates gross pathological damage in abdominal organs and attenuated radiation-induced intestinal histological damage. Therefore, the combination of PS and MF effectively alleviated radiation-induced intestinal injury in the mouse and minipig models. We believe that the combined use of PS and MF is a promising therapeutic approach for treating radiation-induced intestinal injury.
- Subjects
UNITED States. Food &; Drug Administration; INTESTINAL injuries; LABORATORY mice; ANIMAL disease models; TYPE 2 diabetes; NUCLEAR accidents; PRAVASTATIN; FUKUSHIMA Nuclear Accident, Fukushima, Japan, 2011
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 23, p14827
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms232314827