title: Mitigation of radiation-induced hematopoietic injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice.
abstract: Protection of the hematopoietic system from radiation damage, and/or mitigation of hematopoietic injury are the two major strategies for developing medical countermeasure agents (MCM) to combat radiation-induced lethality. In the present study, we investigated the potential of 7, 8-diacetoxy-4-methylthiocoumarin (DAMTC) to ameliorate radiation-induced hematopoietic damage and the associated mortality following total body irradiation (TBI) in C57BL/6 mice. Administration of DAMTC 24 hours post TBI alleviated TBI-induced myelo-suppression and pancytopenia, by augmenting lymphocytes and WBCs in the peripheral blood of mice, while bone marrow (BM) cellularity was restored through enhanced proliferation of the stem cells. It stimulated multi-lineage expansion and differentiation of myeloid progenitors in the BM and induced proliferation of splenic progenitors thereby, facilitating hematopoietic re-population. DAMTC reduced the radiation-induced apoptotic and mitotic death in the hematopoietic compartment. Recruitment of pro-inflammatory M1 macrophages in spleen contributed to the immune-protection linked to the mitigation of hematopoietic injury. Recovery of the hematopoietic compartment correlated well with mitigation of mortality at a lethal dose of 9 Gy, leading to 80% animal survival. Present study establishes the potential of DAMTC to mitigate radiation-induced injury to the hematopoietic system by stimulating the re-population of stem cells from multiple lineages.
authors.affiliation: Division of Metabolic Cell Signalling Research, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, India.|Department of Zoology, University of Delhi, Delhi 110007, India.
authors.forename: Kavya
authors.initials: K
authors.lastname: Venkateswaran
authors.affiliation: Department of Zoology, University of Delhi, Delhi 110007, India.
authors.forename: Anju
authors.initials: A
authors.lastname: Shrivastava
authors.affiliation: Division of Metabolic Cell Signalling Research, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, India.
authors.forename: Paban K
authors.initials: PK
authors.lastname: Agrawala
authors.affiliation: Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Prasad
authors.affiliation: Division of Metabolic Cell Signalling Research, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, India.
authors.forename: Namita
authors.initials: N
authors.lastname: Kalra
authors.affiliation: Division of Metabolic Cell Signalling Research, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, India.
authors.forename: Parvat R
authors.initials: PR
authors.lastname: Pandey
authors.affiliation: Division of Metabolic Cell Signalling Research, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, India.
authors.forename: Kailash
authors.initials: K
authors.lastname: Manda
authors.affiliation: Department of Biochemistry, VP Chest Institute, University of Delhi, Delhi 110007, India.
authors.forename: Hanumantharao G
authors.initials: HG
authors.lastname: Raj
authors.affiliation: Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.affiliation: Division of Metabolic Cell Signalling Research, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, India.|Central Research Facility, Sri Ramachandra University, Porur, Chennai 600116, India.
authors.forename: Bilikere S
authors.initials: BS
authors.lastname: Dwarakanath
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003374:Coumarins / Q000494:pharmacology*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D053208:Kaplan-Meier Estimate; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: C540361:7,8-diacetoxy-4-methylthiocoumarin; D003374:Coumarins