Protective effects of new aryl sulfone derivatives against radiation-induced hematopoietic injury

J Radiat Res. 2020 May 22;61(3):388-398. doi: 10.1093/jrr/rraa009.

Abstract

The hematopoietic system is sensitive to radiation. In this research, new aryl sulfone derivatives (XH-201 and XH-202) containing a nitrogen heterocycle were designed and synthesized and their radio-protective efficacies with regard to the hematopoietic system were evaluated. XH-201 administration significantly increased the survival rate of mice after 8.0 Gy total body irradiation (TBI). The results showed that XH-201 treatment not only increased the white blood cells, platelets counts and the percentage of hematopoietic progenitor cells and hematopoietic stem cells in mice exposed to 4.0 Gy TBI but also decreased DNA damage, as determined by flow cytometric analysis of histone H2AX phosphorylation. In addition, our data demonstrated that XH-201 decreased the mitochondrial reactive oxygen species (ROS) levels in hematopoietic cells. Overall, these data suggest that XH-201 is beneficial for the protection of the hemoatopoietic system against radiation-induced injuries.

Keywords: aryl sulfone derivatives; hematopoietic cells; radioprotection.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • DNA Damage / radiation effects
  • Flow Cytometry
  • Hematopoietic Stem Cells / radiation effects*
  • Histones / chemistry
  • Histones / metabolism
  • Leukocytes, Mononuclear / radiation effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitrogen / chemistry
  • Oxidative Stress
  • Phosphorylation
  • Radiation Injuries / therapy*
  • Radiation-Protective Agents / pharmacology*
  • Reactive Oxygen Species
  • Sulfones / pharmacology*
  • Whole-Body Irradiation

Substances

  • H2AX protein, human
  • Histones
  • Radiation-Protective Agents
  • Reactive Oxygen Species
  • Sulfones
  • Nitrogen