Furazolidone Increases Survival of Mice Exposed to Lethal Total Body Irradiation through the Antiapoptosis and Antiautophagy Mechanism.

Shumei Ma,Xiaodong Liu,Lin Liu,Ping Li,Hao Feng,Yi Liu,Minghua Ren,Zhao Jin,Zhujun Tian,Ana Lloret

doi:10.1155/2021/6610726

Abstract

Exposure to total body irradiation (TBI) causes dose- and tissue-specific lethality. However, there are few effective and nontoxic radiation countermeasures for the radiation injury. In the current study, mice were pretreated with a traditional antimicrobial agent, FZD, before TBI; the protective effects of FZD on radiation injury were evaluated by using parameters such as the spleen index and thymus index, immunohistochemical staining of intestinal tissue, and frequency of micronuclei in polychromatophilic erythrocytes of bone marrow. The intestinal epithelial cell line IEC-6 was used to investigate the underlying mechanisms. Our results indicated that FZD administration significantly improved the survival of lethal dose-irradiated mice, decreased the number of micronuclei, upregulated the number of leukocytes and immune organ indices, and restored intestinal integrity in mice after TBI. TUNEL and western blot showed that FZD protected intestinal tissue by downregulating radiation-induced apoptosis and autophagy. Meanwhile, FZD protected IEC-6 cells from radiation-induced cell death by inhibiting apoptosis and autophagy. To sum up, FZD protected against radiation-induced cell death both in vitro and in vivo through antiapoptosis and antiautophagy mechanisms.

Highlights

With the rapid development of nuclear technology and the extensive application of nuclear medicine, ionizing radiation (IR) is increasing the health risk, and a series of pathological changes might occur and cause tissue damage and even lead to death
The median lethal dose of total body irradiation (TBI) in mice was estimated by overall survival after different doses of irradiation. 40 mice were randomly averagely divided into 4 groups and, respectively, exposed to 2 Gy, 4 Gy, 8 Gy, and 12 Gy disposable TBI
Mice were divided into 4 groups and treated with TBI+saline, TBI+60 mg/kg FZD, TBI+100 mg/kg FZD, and TBI+140 mg/kg FZD by intragastric administration

Summary

Introduction

With the rapid development of nuclear technology and the extensive application of nuclear medicine, ionizing radiation (IR) is increasing the health risk, and a series of pathological changes might occur and cause tissue damage and even lead to death. Exposure to high-dose radiation induces acute radiation syndrome (ARS), manifested by DNA damage, cell death, organ and tissue damage, and so on [1]. When the digestive system is severely damaged, acute gastrointestinal syndrome (AGS) is the predominant cause of death within the first week after IR exposure [6], and AGS is characterized by mucosal epithelium injury and the loss of gastrointestinal function. The current study has shown the ability of FZD to inhibit proliferation and induce cell death and differentiation in human leukemia cells [10]. The effect of FZD on TBI-induced tissue injury and lethality will be analyzed

Materials and Methods

Results

Discussion

Freq G1