Metformin Protects the Rat Small Intestine Against Radiation Enteritis

Abstract

Background: Although radiotherapy is a common choice for cancer therapy, various types of toxicities in irradiated normal tissues limit the received dose by tumor cells. The gastrointestinal tract is one of the most sensitive organs to the detrimental effects of radiation. As a result of a high dose of ionizing radiation, acute morphological changes to the intestine are observed within days to weeks. Objectives: In this study, we aimed to evaluate the protective effects of metformin against radiation-induced small intestine injury. Methods: In this experimental study, we used 20 male Wistar albino rats in four groups including control, 10 Gy irradiation, metformin alone, and metformin with radiation. Metformin was orally administered 24 hours before irradiation for three days. Afterward, the rats were sacrificed 3.5 days after radiation exposure. The duodenum and jejunum were removed and fixed in 10% formalin. For light microscopic studies, duodenum and jejunum specimens were embedded in paraffin and then, 5 µm sections were obtained and stained with hematoxylin and eosin. Results: Irradiation led to a significant shortening of villi and mucosal atrophy, edema and inflammation in villi, and epithelial degeneration. When rats were treated with metformin, these damages were ameliorated in both duodenum and jejunum. Conclusions: In this study, we showed that metformin can be proposed for the radioprotection of the small intestine. This property is very obvious, especially for damages to the villous and epithelium. Although further studies are needed for exploring the protective mechanisms of metformin in this organ, it is possible that suppressing the production of free radicals via mitochondria or inflammatory responses plays a role.