title: CCM-AMI, a Polyethylene Glycol Micelle with Amifostine, as an Acute Radiation Syndrome Protectant in C57BL/6 Mice.
abstract: Acute radiation syndrome results from radiation exposure, such as in accidental nuclear disasters. Safe and effective radioprotectants, mitigators, and treatment drugs must be developed as medical countermeasures against radiation exposure. Here, the authors evaluated CCM-Ami, a novel polyethylene glycol micelle encapsulated with amifostine, for its radioprotective properties after total-body irradiation from a 60Co source. Male C57BL/6 mice (6-8 wk old) were intravenously injected with 45 mg kg(-1) of CCM-Ami 90 min before exposure to 7.2 and 8.5 Gy irradiation at a dose rate of 0.04 Gy min(-1). Both survival benefit and hematopoietic protection were observed after prophylactic CCM-Ami administration when compared with the effects measured in excipient control and amifostine groups. Pharmacokinetic results showed that after the intravenous injection, the plasma concentration of WR-1065, the active form of amifostine, was higher in CCM-Ami-treated mice than in amifostine-treated mice. These findings suggest that CCM-Ami-mediated hematopoietic protection plays a key role in enhancing survival of mice exposed to radiation toxicity and thus indicate that CCM-Ami is a radioprotectant that can be used safely and effectively in nuclear disasters.
authors.affiliation: *Institute of Toxicology, College of Medicine, †Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan; ‡Institute of Basic Medical Sciences, National Cheng Kung University, College of Medicine, Tainan, Taiwan; §Department of Occupational Therapy, I-Shou University, Kaohsiung, Taiwan; §§Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; **Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; ††Department of Hematology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.forename: Jen-Ling
authors.initials: JL
authors.lastname: Wang
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Liao
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chang
authors.forename: Leong-Perng
authors.initials: LP
authors.lastname: Chan
authors.forename: Johnson
authors.initials: J
authors.lastname: Lin
mesh_terms: D054508:Acute Radiation Syndrome / Q000097:blood / Q000517:prevention & control*; D004999:Amifostine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D008297:Male; D008624:Mercaptoethylamines / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D011092:Polyethylene Glycols; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014916:Whole-Body Irradiation
chemical_list: D008624:Mercaptoethylamines; D008823:Micelles; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D011092:Polyethylene Glycols; D004999:Amifostine