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

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

Acknowledgments

The authors thank Drs. Yanan Zhang and Jianghua Wan for their kind help. We are grateful to the HIRFL-CSR crew for providing the heavy ion beams.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

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. 10979062) and Jufang Wang (No. U1232125 & 31270895).