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

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.

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

“…Aspirin ameliorates radiation-induced kidney and lung damage and reduces post-irradiation chromosomal aberrations [ 286 ]. A recent meta-analysis of randomized controlled trials indicates that acetylsalicylic acid reduces the overall risk of recurrence and mortality of colorectal cancer and/or colorectal adenomas, which increases the interest in its possible use as a radioprotector/radiosensitizer [ 287 ]. Flurbiprofen showed radioprotection in clinical studies, e.g., delaying the onset of mucositis and reducing its severity after radiotherapy in head and neck cancer patients, although the overall severity or duration of mucositis was not improved [ 288 ].…”

Schisandrin A Suppresses Inflammation in DSS-induced IBD Mice and H2O2-induced MODE-K Cells through Wnt/β-Catenin Signaling

“…Mice were weighed daily throughout the experiment. On the last day of the investigation, mice were placed in a closed environment, and fecal samples were taken for 3 h. Next, disease activity index (DAI), fecal water content, and loose stool rate were determined as described previously (Han et al, 2019; Ma et al, 2021a; Yang et al, 2022; Zhan et al, 2022). Mice were anesthetized with 20% chloral hydrate, and the myeloperoxidase (MPO) activity in extracted colon tissue was assessed based on the requirements of a specific kit.…”

Radioprotectors, Radiomitigators, and Radiosensitizers

“…In vitro, FZD treatment reduced unstable chromosomal aberrations (CAs) (such as acentric and dicentric chromosomes (DC)), chromosome breaks, and radiosensitivity of intestinal epithelial cells. Ma et al [25] showed that FZD treatment significantly improved the sur-vival of lethal dose-irradiated mice, decreased the number of micronuclei (MN), increased the number of leukocytes and immune organ indices, and reversed the apoptosis and autophagy in the small intestine, thus restoring intestinal integrity. Their experiments showed that irradiation resulted in villous shortening and crypt dilation accompanied by epithelial atrophy or slough, and even marked edema and inflammatory cell infiltration, and how FZD significantly induced damage recovery.…”

“…Flurbiprofen also showed radioprotection in clinical studies, e.g., delaying the onset of mucositis and reducing its severity after RT in 12 head and neck cancer patients, although the overall severity or duration of mucositis was not improved [138]. A recent meta-analysis of randomized controlled trials indicates that aspirin reduces the overall risk of recurrence and mortality of colorectal cancer and/or colorectal adenomas, which increases the interest in its possible use as a radiomitigator [24,25]. However, nonselective COXi are known to cause undesirable side effects including GI ulcers and bleeding when taken for continued periods of time.…”