GANRA-5 protects mice from X-ray irradiation-induced dysfunction of the immune system

Free Radic Res. 2014 Aug;48(8):875-82. doi: 10.3109/10715762.2014.919389. Epub 2014 May 27.

Abstract

Ionizing radiation produces reactive oxygen species (ROS), which cause damage to cells. We have synthesized a class of ROS scavengers and found that one of them, named GANRA-5, exhibits high radio-protective effects against both heavy ion irradiation and X-rays, while at the same time displaying low levels of toxicity. Pre-administration with an effective dose of GANRA-5 reduces radiation-induced damage to tissues and increases the survival rate of exposed mice. In this study, we evaluated the changes to the immune system via X-ray irradiation, and investigated how pre-administration of GANRA-5 exhibited preventative characteristics. Compared to the irradiated control groups, GANRA-5 treatment significantly reduced the radiation-induced spleen shrinkage and pathological changes. Moreover, pretreatment with GANRA-5 significantly (p < 0.01) enhanced the cellular immune response, which was characterized by higher peritoneal macrophage as well as splenocyte survival, and a higher ratio of CD4(+)/CD8(+) T lymphocytes. In addition, GANRA-5 treatment before whole body irradiation significantly improved the humoral response (p < 0.01) as indicated by the higher antibody titers of IgG, IgA, and IgM. Furthermore, GANRA-5 treatment significantly (p < 0.01) countered radiation-induced decreases in the titers of serum IL-2 and IL-4 when compared to irradiated but untreated control groups. In summary, these findings indicate that GANRA-5 provides effective protection to the immune system against X-ray-induced immunosuppression.

Keywords: GANRA-5; X-rays; immunosuppression; radioprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / chemistry
  • Benzoates / pharmacology
  • Immune System / drug effects*
  • Immune System / radiation effects*
  • Male
  • Mice
  • Radiation Dosage
  • Radiation-Protective Agents / chemistry
  • Radiation-Protective Agents / pharmacology*
  • Random Allocation
  • Reactive Oxygen Species / metabolism*
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / pathology
  • Spleen / radiation effects
  • X-Rays

Substances

  • Benzoates
  • Radiation-Protective Agents
  • Reactive Oxygen Species