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

Free Radic Res. 2014 Jun;48(6):670-8. doi: 10.3109/10715762.2014.898843. Epub 2014 Mar 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • DNA Breaks, Double-Stranded / drug effects
  • DNA Breaks, Double-Stranded / radiation effects*
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Genomic Instability / drug effects
  • Genomic Instability / radiation effects*
  • Heavy Ions / adverse effects
  • Histones
  • Humans
  • Malondialdehyde / analysis
  • Mice
  • Micronucleus Tests
  • Microwaves / adverse effects
  • Oxazolone / analogs & derivatives
  • Oxazolone / chemistry
  • Oxazolone / pharmacology*
  • Radiation-Protective Agents / chemistry
  • Radiation-Protective Agents / pharmacology*
  • Superoxide Dismutase / analysis
  • Ultraviolet Rays / adverse effects
  • X-Rays / adverse effects

Substances

  • Free Radical Scavengers
  • Histones
  • Radiation-Protective Agents
  • gamma-H2AX protein, mouse
  • Oxazolone
  • Malondialdehyde
  • Superoxide Dismutase