GANRA-5 protects both cultured cells and mice from various radiation types by functioning as a free radical scavenger

Abstract

The radio-protective effects of the oxazolone derivative chemical compound 4-(4-methoxy-3-methoxyphenyl-methyl)-2-phenyl- 5(4H)-oxazolone (GANRA-5) against different types of radiation including X-rays, carbon ion beams, microwaves and ultraviolet light (UV) were studied. Cell proliferation/cytotoxicity assay and colony-forming assay were conducted to evaluate the toxicity of GANRA-5. To test its influence on the induction of double-stranded break (DSB) formation and genomic instability, γH2AX focus-forming assay as well as cytokinesis-block micronucleus assay was utilized. Our results indicate that GANRA-5 exhibits low toxicity, while providing high radio-protective effects for MRC-5 cells against different types of radiation. We also found that GANRA-5 acts as a free radical scavenger. Our animal studies provided evidence that GANRA-5 significantly increases the survival rate of mice after X-ray irradiation. Analyses of hemogram, visceral index and detection of superoxide dismutase (SOD) and malondialdehyde (MDA) in the viscera indicate both low toxicity of GANRA-5, combined with its ability to shield radiation risk. In conclusion, our results suggest that GANRA-5 has the potential to be used as a safe and efficient radio-protectant.

Keywords::

• radio-protectors
• GANRA-5
• reactive oxygen species
• free radicals
• radiation

Acknowledgements

The authors thank Drs. Yanan Zhang and Jianghua Wan for their assistance with the experiment procedures. We are grateful to the HIRFL-CSR crew for providing excellent technical assistance with the operation of the heavy ion beams.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

This work was supported by grants of the Major State Basic Research Development Program of China (973 Program, No. 2010CB834201), the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDA01040411), and the National Natural Science Foundations of China awarded to Guangming Zhou (No. 11335011, 31370846 and 10979062) and Jufang Wang (No. U1232125 & 31270895).