The effects of single subcutaneous injection of cadmium chloride on haemopoiesis in normal (non- irradiated) or irradiated mice were investigated. Cadmium doses used ranged from 1-8 mg/kg body weight. Twenty-four hours after treatment with cadmium (doses from 3 to 8 mg/kg) there were no significant changes in bone marrow cellularity and the granulocyte-macrophage progenitor cell (GM- CFC) number per femur in non-irradiated female ICR mice. Similarly, during the 30-day postinjection period bone marrow cellularity and marrow GM-CFC number in mice treated with a cadmium dose of 5 mg/kg were not significantly different from the control values. Cadmium significantly reduced the lethal effects of gamma rays. In addition, increasing the doses of cadmium administered 24 h prior to sublethal irradiation increased the number of endogenous haemopoietic stem cells (endoCFU-S) in a concentration-dependent manner. Pretreatment with cadmium also decreased the radiation damage to endoCFU-S and haemopoietic progenitor cells committed to granulocyte/macrophage development (GM-CFC). The survival of stem cells was higher and the regeneration of cellularity and GM-CFC of irradiated bone marrow was accelerated in mice pretreated with 5 mg Cd/kg body weight in comparison with saline-injected mice.
The effect of administration of cadmium alone in non-irradiated mice as well as the effect of preirradiation administration of cadmium on the reparation processes of haemopoiesis were investigated in mice irradiated by a dose of 7.5 Gy. The pre-irradiation administration of cadmium accelerated the reparation processes in the bone marrow and spleen as well as the number of leukocytes and thrombocytes in the peripheral blood. The administration of cadmium alone caused a temporary weight decrease of the thymus and reduced number of erythrocytes, reticulocytes and haemoglobin values in the peripheral blood. The temporary rapid increase in the number of leukocytes on the 21st day after cadmium administration was investigated.
The effects of diclofenac, an inhibitor of prostaglandin synthesis, were studied on the acute radiation syndrome elicited in mice by fractional irradiation. Several haematological parameters were evaluated in mice irradiated with 5x2 Gy and 3x, 4x, or 5x3 Gy (intervals between fractions 24 h) from a 60Co gamma-ray source. The animals were treated with diclofenac either before each fraction or only once before the last fraction. The survival of mice was recorded after the irradiation regimen of 5x3 Gy followed by a "top-up" dose of 3.5 Gy given 24 h after the last radiation fraction. Statistically significant enhancement of the endogenous spleen colony formation and of leukopoiesis was found in mice treated with diclofenac repeatedly, as compared with both saline-treated irradiated controls and animals administered a single diclofenac dose, if a sublethal total radiation dose had been accumulated. However, following accumulation of a lethal total radiation dose, slightly impaired survival was observed in mice given diclofenac. It follows from the results that diclofenac is a suitable drug for enhancing leukopoiesis impaired by sublethal fractionated irradiation. Nevertheless, undesirable side effects of this drug negatively influence the survival of experimental animals following a lethal accumulated radiation dose.
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.