KR-31831 improves survival and protects hematopoietic cells and radiosensitive tissues against radiation-induced injuries in mice.

Abstract

This study explored the radioprotective effects and possible underlying mechanisms of KR-31831 against radiation-induced injury in a mouse model. KR-31831 (30 and 50 mg/kg) was administered to mice 24 h and 30 min before exposure to a single lethal or sublethal dose of whole-body irradiation (WBI) (7 or 4 Gy, respectively). These animals were then evaluated for changes in mortality, various hematological and biochemical parameters, and histological features in response to these treatments. In addition, RNA sequencing was used to profile the radiation-induced transcriptomic response in the bone marrow cells. The results showed that KR-31831 dose-dependently prolonged the 30-day survival period and prevented damage to radiation-sensitive organs, such as the intestine and testis, in response to WBI. Damage to the hematopoietic system was also notably improved in the KR-31831-treated mice, as evidenced by an increase in bone marrow and peripheral blood cells, as well as recovery of the histopathological characteristics of the bone marrow. These protective effects were achieved, at least in part, via the suppression of radiation-induced increases in apoptotic cell death and erythropoietin levels in the plasma. Furthermore, the gene expression profiles of the bone marrow cells of the WBI-treated mice suggested that KR-31831 upregulates the expression of the genes involved in regulating apoptosis and modulating the immune response, both of which are required for protecting the bone marrow. These results suggest the potential therapeutic efficacy of KR-31831 for protection against radiation-induced injury.

• Authors: Jeong Hyun Lee, Hyuna Yi, Ju Hee Lee, Ho Won Seo, Kwang-Seok Oh, Byung Ho Lee
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 146 Pg. 112350 (Feb 2022) ISSN: 1950-6007 [Electronic] France
• PMID: 34952740 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Benzopyrans
• Imidazoles
• KR 31831
• Radiation-Protective Agents

Topics

• Animals
• Benzopyrans (therapeutic use)
• Bone Marrow Cells (drug effects, metabolism, radiation effects)
• Imidazoles (therapeutic use)
• Intestines (drug effects, radiation effects)
• Male
• Mice, Inbred C57BL
• Radiation Injuries (drug therapy, genetics)
• Radiation-Protective Agents (therapeutic use)
• Testis (drug effects, radiation effects)
• Transcriptome (drug effects)
• Whole-Body Irradiation (adverse effects)