Astaxanthin attenuates total body irradiation-induced hematopoietic system injury in mice via inhibition of oxidative stress and apoptosis

Stem Cell Res Ther. 2017 Jan 23;8(1):7. doi: 10.1186/s13287-016-0464-3.

Abstract

Background: The hematopoietic system is especially sensitive to total body irradiation (TBI), and myelosuppression is one of the major effects of TBI. Astaxanthin (ATX) is a powerful natural anti-oxidant with low toxicity. In this study, the effect of ATX on hematopoietic system injury after TBI was investigated.

Methods: Flow cytometry was used to detect the proportion of hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs), the level of intracellular reactive oxygen species (ROS), expression of cytochrome C, cell apoptosis, and NRF2-related proteins. Immunofluorescence staining was used to detect Nrf2 translocation. Western blot analysis was used to evaluate the expression of apoptotic-related proteins. Enzymatic activities assay kits were used to analyze SOD2, CAT, and GPX1 activities.

Results: Compared with the TBI group, ATX can improve radiation-induced skewed differentiation of peripheral blood cells and accelerate hematopoietic self-renewal and regeneration. The radio-protective effect of ATX is probably attributable to the scavenging of ROS and the reduction of cell apoptosis. These changes were associated with increased activation of Nrf2 and downstream anti-oxidative proteins, and regulation of apoptotic-related proteins.

Conclusions: This study suggests that ATX could be used as a potent therapeutic agent to protect the hematopoietic system against TBI-induced bone marrow suppression.

Keywords: Astaxanthin; Cell apoptosis; Hematopoietic stem cells; Ionizing radiation; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Blood Cells / cytology
  • Blood Cells / drug effects
  • Blood Cells / radiation effects
  • Body Weight / drug effects
  • Body Weight / radiation effects
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / radiation effects
  • Cell Differentiation / drug effects
  • Glutathione Peroxidase / metabolism
  • Glutathione Peroxidase GPX1
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic System / drug effects*
  • Hematopoietic System / injuries
  • Hematopoietic System / radiation effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / radiation effects
  • NF-E2-Related Factor 2 / deficiency
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / radiation effects
  • Proto-Oncogene Proteins c-kit / metabolism
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism
  • Whole-Body Irradiation*
  • Xanthophylls / pharmacology

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Reactive Oxygen Species
  • Xanthophylls
  • astaxanthine
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Proto-Oncogene Proteins c-kit
  • Glutathione Peroxidase GPX1
  • Gpx1 protein, mouse