GANRA-5 protects mice from X-ray irradiation-induced dysfunction of the immune system.
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.
Department of Space Radiobiology, Institute of Modern Physics, Chinese Academy of Sciences , Lanzhou , P. R. China.
T
T
Liu
H
H
Pei
D
D
Xu
Y
Y
Zhang
J
J
Wan
X
X
Wu
X
X
Zhang
F
F
Sun
J
J
He
P
P
Li
N
N
Tian
J
J
Wang
W
W
Chen
G
G
Zhou
D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology; D007107:Immune System / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D011829:Radiation Dosage; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D014965:X-Rays
D001565:Benzoates; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species
GANRA-5; X-rays; immunosuppression; radioprotection