title: Amifostine acts upon mitochondria to stimulate growth of bone marrow and regulate cytokines.
abstract: Amifostine is a first-line cytoprotective drug used to prevent radiotherapy-induced or chemotherapy-induced injuries. However, its mechanism of action is not well understood. In this study, freshly harvested bone marrow cells were treated with amifostine and analyzed with a series of mitochondrial indices. In vitro results showed that bone marrow cells treated with amifostine 0.5 h before irradiation (0.5 Gy) experienced several benefits, as compared to vehicle controls, including (1) reduced reactive oxygen species levels, which reduced the production of free radicals; (2) better preservation of mitochondria, as indicated by MitoTracker-positive staining and the increased intensity of staining; (3) reduced apoptosis, as demonstrated by Annexin V staining; and (4) a better proliferation rate, as illustrated by MTT assay. Our in vitro studies showed that amifostine-treated mice exhibited (1) higher ATP production; (2) reduced plasma IL-2 levels, suppressing the immune response triggered by radiotoxicity; and (3) enhanced radiation-induced production of granulocyte colony-stimulating factor. All of these processes benefit recovery from radiation-induced damage.
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.|Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Luqiang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Shanmin
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Liangjie
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.|Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Deping
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.|Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Sadasivan
authors.initials: S
authors.lastname: Vidyasagar
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Okunieff
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, Gainesville, FL, USA. lurongzhang@ufl.edu.
authors.forename: Lurong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016207:Cytokines; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D004999:Amifostine