title: A study of the effect of sequential injection of 5-androstenediol on irradiation-induced myelosuppression in mice.
abstract: Herein, we aimed at examining the therapeutic effects of 5-androstenediol (5-AED), a natural hormone produced in the adrenal cortex, on radiation-induced myelosuppression in C3H/HeN mice. The mice were subjected to whole-body irradiation with a sublethal dose of 5 Gy gamma-irradiation to induce severe myelosuppression, and 5-AED (50 mg/kg) was administered subcutaneously. 5-AED was administrated 1 day before irradiation (pre-treatment) or twice weekly for 3 weeks starting from 1 h after irradiation (post-treatment). Treatment with 5-AED significantly ameliorated the decrease in the peripheral blood neutrophil and platelet populations in irradiated myelosuppressive mice, but had no effect on the lymphocyte population. It also ameliorated hypocellularity and disruption of bone marrow induced by irradiation and led to rapid recovery of myeloid cells. Further, it attenuated the decrease in spleen weight and megakaryocyte and myeloid cell populations in the spleen and promoted multilineage hematopoietic recovery. We found that a single injection of 5-AED produced only a temporary therapeutic effect, while sequential injection of 5-AED after irradiation had a more pronounced and prolonged therapeutic effect and reduced myelosuppression by irradiation. Thus, sequential injection of 5-AED after irradiation has therapeutic potential for radiation-induced myelosuppression when administered continuously and can be a significant therapeutic candidate for the management of acute radiation syndrome, particularly in a mass casualty scenario where rapid and economic intervention is important.
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), 267-2 Jwadong-gil, Jangan-eup, Busan, 619-953, Korea, jskim@dirams.re.kr.
authors.forename: Joong Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Won Suk
authors.initials: WS
authors.lastname: Jang
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Lee
authors.forename: Yeonghoon
authors.initials: Y
authors.lastname: Son
authors.forename: Sunhoo
authors.initials: S
authors.lastname: Park
authors.forename: Seung Sook
authors.initials: SS
authors.lastname: Lee
mesh_terms: D015114:Androstenediol / Q000494:pharmacology*; D000818:Animals; D001772:Blood Cell Count; D001792:Blood Platelets / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects* / Q000528:radiation effects*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005269:Femur / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D005720:Gamma Rays; D007279:Injections, Subcutaneous; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D022423:Myeloid Cells / Q000187:drug effects / Q000528:radiation effects; D009504:Neutrophils / Q000187:drug effects; D011833:Radiation Injuries, Experimental / Q000188:drug therapy; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects
chemical_list: D011837:Radiation-Protective Agents; D015114:Androstenediol