Radioprotective effects of flurbiprofen and its nitroderivative.
Radioprotective effects of two non-steroidal anti-inflammatory drugs, flurbiprofen (FBP) and its novel nitroderivative flurbiprofen 4-nitroxybutylester (NO-FBP), which exhibits decreased gastrointestinal toxicity, were compared in mice. The drugs were administered in equimolar single doses, 2 hours before whole-body gamma-irradiation of the animals. After a sublethal radiation dose of 6.5 Gy, significantly increased numbers of endogenous haemopoietic spleen colonies and enhanced granulopoiesis were found in mice given either FBP or NO-FBP, when compared to vehicle-treated controls. There were no differences in the effectiveness of either drug to enhance postirradiation haemopoietic recovery. Survival of FBP- or NO-FBP-treated mice subjected to a lethal dose of 9.5 Gy was slightly but insignificantly enhanced, both drugs showing the same effect. These results clearly indicate the ability of both drugs to enhance haemopoietic recovery after sublethal radiation exposure and the absence of unfavourable effects under higher radiation doses. Because of its lower potential for gastrointestinal damage, NO-FBP seems to be a promising drug, which can find a use in the protection of postirradiation myelosuppression.
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno.
L
L
Juchelková
M
M
Hofer
M
M
Pospísil
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I
Pipalová
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D016019:Survival Analysis; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011837:Radiation-Protective Agents; C095631:nitroflurbiprofen; D005480:Flurbiprofen