Mn(III) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin mitigates total body irradiation-induced long-term bone marrow suppression

Hongliang Li, Yong Wang, Senthil K. Pazhanisamy, Lijian Shao, Ines Batinic-Haberle, Aimin Meng, Daohong Zhou

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Our recent studies showed that total body irradiation (TBI) induces long-term bone marrow (BM) suppression in part by induction of hematopoietic stem cell (HSC) senescence through reactive oxygen species (ROS). In this study, we examined if Mn(III) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin (MnTE), a superoxide dismutase mimetic and potent antioxidant, can mitigate TBI-induced long-term BM injury in a mouse model. Our results showed that post-TBI treatment with MnTE significantly inhibited the increases in ROS production and DNA damage in HSCs and the reduction in HSC frequency and clonogenic function induced by TBI. In fact, the clonogenic function of HSCs from irradiated mice after MnTE treatment was comparable to that of HSCs from normal controls on a per-HSC basis, suggesting that MnTE treatment inhibited the induction of HSC senescence by TBI. This suggestion is supported by the finding that MnTE treatment also reduced the expression of p16 Ink4a (p16) mRNA in HSCs induced by TBI and improved the long-term and multilineage engraftment of irradiated HSCs after transplantation. Therefore, the results from this study demonstrate that MnTE has the potential to be used as a therapeutic agent to mitigate TBI-induced long-term BM suppression by inhibiting ionizing radiation-induced HSC senescence through the ROS-p16 pathway.

Original languageEnglish (US)
Pages (from-to)30-37
Number of pages8
JournalFree Radical Biology and Medicine
Volume51
Issue number1
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

Keywords

  • Free radicals
  • Hematopoietic stem/progenitor cells
  • Ionizing radiation
  • Manganese(III) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin
  • Oxidative stress
  • Radioprotection
  • superoxide dismutase mimetic

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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