Prophylactic administration of podophyllotoxin and rutin combination assists the revival of radiation-induced hematopoietic suppression in lethally irradiated mice

Biochem Biophys Res Commun. 2021 Apr 16:549:214-220. doi: 10.1016/j.bbrc.2021.02.085. Epub 2021 Mar 8.

Abstract

Hematopoietic syndrome contributes to mortality after exposure to high doses of low LET radiation. In this context, we have earlier demonstrated the potential of G-003 M (a combination of podophyllotoxin and rutin) in alleviating radiation-induced bone marrow suppression. Similarly, we here demonstrate that G-003 M protected mice from death (>83% protection) and increased the populations of CD 34 (Cluster of differentiation 34) as well as CD 117 (Cluster of differentiation 117) positive cell population and their colony forming capacity. This was accompanied with increase in the serum titre of granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF). Interestingly, G-003 M lowered down the titre of fms-like tyrosine kinase (Flt-3) ligands. Our results furthermore demonstrates that G-003 M facilitated the nuclear translocation of β-catenin and upregulated the expression of Wnt 10b. Conditioning of animal with G-003 M activated the expression of survivin, inhibited the activation of Caspase-3 in CD 34/117+ progenitor stem cells and protected the bone marrow vascularity and splenic colonies in lethally irradiated animals, which collectively promoted hemopoietic recovery in lethally irradiated mice.

Keywords: Apoptosis; Bone marrow; Cytokine; Gamma radiation; Podophyllotoxin; Radio protector.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bone Marrow / drug effects
  • Bone Marrow / radiation effects
  • Cell Proliferation / drug effects
  • Drug Therapy, Combination
  • Female
  • Gamma Rays*
  • Hematopoiesis / drug effects*
  • Hematopoiesis / radiation effects*
  • Hematopoietic Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Podophyllotoxin / administration & dosage
  • Podophyllotoxin / pharmacology*
  • Rutin / administration & dosage
  • Rutin / pharmacology*
  • Up-Regulation / drug effects
  • Wnt Signaling Pathway / drug effects

Substances

  • Rutin
  • Podophyllotoxin