Radiation research, 2015-04, Vol.183 (4), p.465
2015
Details
- Autor(en) / Beteiligte
- Titel
- Mitigation of the hematopoietic and gastrointestinal acute radiation syndrome by octadecenyl thiophosphate, a small molecule mimic of lysophosphatidic acid
- Ist Teil von
- Radiation research, 2015-04, Vol.183 (4), p.465
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2015
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- We have previously demonstrated that the small molecule octadecenyl thiophosphate (OTP), a synthetic mimic of the growth factor-like mediator lysophosphatidic acid (LPA), showed radioprotective activity in a mouse model of total-body irradiation (TBI) when given orally or intraperitoneally 30 min before exposure to 9 Gy γ radiation. In the current study, we evaluated the effects of OTP, delivered subcutaneously, for radioprotection or radiomitigation from -24 h before to up to +72 h postirradiation using a mouse TBI model with therapeutic doses at around 1 mg/kg. OTP was injected at 10 mg/kg without observable toxic side effects in mice, providing a comfortable safety margin. Treatment of C57BL/6 mice with a single dose of OTP over the time period from -12 h before to +26 h after a lethal dose of TBI reduced mortality by 50%. When administered at +48 h to +72 h postirradiation (LD50/30 to LD100/30), OTP reduced mortality by ≥34%. OTP administered at +24 h postirradiation significantly elevated peripheral white blood cell and platelet counts, increased crypt survival in the jejunum, enhanced intestinal glucose absorption and reduced endotoxin seepage into the blood. In the 6.4-8.6 Gy TBI range using LD50/10 as the end point, OTP yielded a dose modification factor of 1.2. The current data indicate that OTP is a potent radioprotector and radiomitigator ameliorating the mortality and tissue injury of acute hematopoietic as well as acute gastrointestinal radiation syndrome.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1938-5404DOI: 10.1667/RR13830.1Titel-ID: cdi_pubmed_primary_25807318
- Format
- –
- Schlagworte
- Acute Radiation Syndrome - prevention & control, Adaptor Proteins, Signal Transducing - metabolism, Animals, Antigens, CD34 - metabolism, ATPases Associated with Diverse Cellular Activities, Biological Transport - drug effects, Biological Transport - radiation effects, Biomimetic Materials - adverse effects, Biomimetic Materials - pharmacokinetics, Biomimetic Materials - pharmacology, Cell Survival - drug effects, Cell Survival - radiation effects, Clone Cells - cytology, Clone Cells - drug effects, Clone Cells - radiation effects, Dose-Response Relationship, Drug, Female, Gastrointestinal Tract - drug effects, Gastrointestinal Tract - metabolism, Gastrointestinal Tract - microbiology, Gastrointestinal Tract - radiation effects, Glucose - metabolism, HEK293 Cells, Hematopoiesis - drug effects, Hematopoiesis - radiation effects, Hematopoietic Stem Cells - cytology, Hematopoietic Stem Cells - drug effects, Hematopoietic Stem Cells - radiation effects, Humans, Leukocyte Count, LIM Domain Proteins - metabolism, Lysophospholipids - metabolism, Mice, Mice, Inbred C57BL, Organophosphorus Compounds - adverse effects, Organophosphorus Compounds - pharmacokinetics, Organophosphorus Compounds - pharmacology, Phosphoproteins - metabolism, Platelet Count, Proteasome Endopeptidase Complex, Radiation-Protective Agents - adverse effects, Radiation-Protective Agents - pharmacokinetics, Radiation-Protective Agents - pharmacology, Sodium-Hydrogen Exchangers - metabolism, Transcription Factors - metabolism, Whole-Body Irradiation - adverse effects