Protective effect of the antioxidative peptide SS31 on ionizing radiation-induced hematopoietic system damage in mice

Blood Cells Mol Dis. 2019 Jul:77:82-87. doi: 10.1016/j.bcmd.2019.04.001. Epub 2019 Apr 7.

Abstract

Ionizing radiation (IR) causes severe damage to the hematopoietic system; thus, it is necessary to explore agents or compounds that can reduce this damage. SS31 is a mitochondria-targeted peptide that can scavenge cellular reactive oxygen species (ROS) and inhibit the production of mitochondrial ROS. Therefore, in this study, we discuss the protective effect of SS31 on IR-induced hematopoietic system damage. Our results showed that treatment with 6 mg/kg SS31 elevated the survival rate of lethally irradiated mice and increased the numbers of white blood cells, red blood cells, hemoglobin and platelets in mice exposed to 4 Gy whole-body irradiation. In addition, SS31 administration improved the number of hematopoietic stem/progenitor cells (HSPCs) and the self-renewal and reconstitution abilities of these cells in irradiated mice. The elevation of ROS levels is the main cause of IR-induced hematopoietic system damage, and SS31 can effectively reduce the ROS level in HSPCs. The above results suggest that SS31 can protect the hematopoietic system from radiation-induced damage by reducing cellular ROS levels.

Keywords: Hematopoietic system; Ionizing radiation; Reactive oxygen species; SS31.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • DNA Damage / drug effects
  • DNA Damage / radiation effects
  • Disease Models, Animal
  • Hematopoiesis / drug effects*
  • Hematopoiesis / radiation effects*
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / radiation effects*
  • Male
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondria / radiation effects
  • Oligopeptides / pharmacology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Radiation Dosage
  • Radiation Injuries, Experimental / blood
  • Radiation Injuries, Experimental / mortality
  • Radiation, Ionizing*
  • Reactive Oxygen Species / metabolism
  • Stem Cells
  • Survival Rate
  • Whole-Body Irradiation

Substances

  • Antioxidants
  • Oligopeptides
  • Reactive Oxygen Species
  • arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide