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.
We have recently demonstrated that the combined administration of dipyridamole and adenosine monophospate to mice induces radioprotective effects in terms of postirradiation haemopoietic recovery in animals irradiated with a single dose. The aim of the present experiments was to investigate the radioprotective ability of the drug combination under conditions of fractionated radiation treatment. It has been shown that administration of drugs either 15 or 60 min before each of the five daily 3-Gy doses of gamma-radiation enhances haemopoietic recovery and survival of mice exposed to an additional "top-up" dose of 3.5 Gy. Furthermore, it has been ascertained that the regimen using administration of the drugs 60 min prior to irradiation is more effective than administration of the drugs 15 min prior to irradiation. Due to the evidence that administration of the drugs 15 min prior to irradiation protects the organism mainly via mechanisms of systemic hypoxia while the pretreatment 60 min before irradiation avoids the role of hypoxia and mainly induces cell proliferation effects, our results suggest a more effective protective role of mechanisms stimulating haemopoiesis under conditions of fractionated radiation. The data may provide a basis for more rational use of radioprotection in fractionated radiation regimens.