Combined Administration of Pravastatin and Metformin Attenuates Acute Radiation-Induced Intestinal Injury in Mouse and Minipig Models

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.

Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

“…In animal experiments, Kim et al [ 137 ] used a combination of PS and MF in a minipig model and found that the combined treatment could attenuate radiation-induced intestinal histological damage, significantly increase the survival rate of the lethal dose radiation model, and achieve better therapeutic effects. Najafi et al [ 138 ] investigated the possible radioprotection of the ileum and colon in rats using a combination of melatonin and metformin.…”

Oral Administration of Probiotic Spore Ghosts for Efficient Attenuation of Radiation-Induced Intestinal Injury

“…[5,6] Exposure of small intestine to ionizing radiation can lead to serious gastrointestinal dysfunction, such as vomiting, abdominal pain, diarrhea, infection, perforation, and even death. [7] To date, there are few effective countermeasures for intestinal radioprotection in clinical.…”

Oral administration of probiotic spore ghosts for efficient attenuation of radiation-induced intestinal injury

“…Small intestine is one of the most radiation-sensitive organs with large organ volume and is a major injury tissue during abdominal and pelvic radiation therapy [5,6]. Exposure of small intestine to ionizing radiation can lead to serious gastrointestinal dysfunction, such as vomiting, abdominal pain, diarrhea, infection, perforation, and even death [7]. To date, there are few effective countermeasures for intestinal radioprotection in clinical.…”