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

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 beta-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. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

The study demonstrates that G-003 M shows significant protective effects against radiation-induced mortality in mice, enhancing specific cell populations and colony-forming capabilities, while also reducing the levels of certain cytokines. Additionally, G-003 M promotes the expression of specific proteins, protects bone marrow vascularity and splenic colonies, contributing to hematopoietic recovery.