Why the study?
Does administration of amifostine alone or with dexrazoxane prevent doxorubicin-mediated bone damage in male rat pups?
Does administration of amifostine alone or with dexrazoxane prevent doxorubicin-mediated bone damage in male rat pups?
In a rat model, cardioprotectants like dexrazoxane and amifostine used with doxorubicin have complex effects on vertebral bone quality, with most combinations decreasing bone mineral density.
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Rat pup data should not alter cardioprotectant use; leaves open whether amifostine or dexrazoxane protect bone in children.
Doxorubicin (DOX) is widely used in combination cocktails for treatment of childhood hematological cancers and solid tumors. A major factor limiting DOX usage is DOX-induced cardiotoxicity. However, it is not known whether protectants like dexrazoxane (DXR) and amifostine (AMF) can prevent DOX-mediated bone damage. The present study investigated whether administration of AMF alone or in combination with DXR would prevent any DOX-mediated bone damage. Male rat pups were treated with DOX, DXR, AMF, and their combinations. On neonate day 38, the bone mineral density (BMD), bone mineral content (BMC) and the micro-architecture of the lumbar vertebrae were analyzed. We have shown that when male rats are treated with DOX, DXR, DOX+DXR, AMF, DOX+AMF or DOX+DXR+AMF, there is a decrease in lumbar vertebral BMD (p<0.05). Furthermore, the relative bone volume (BV/TV) was decreased by DXR, DOX+DXR, and DOX+AMF treatments. Interestingly, DOX+AMF significantly increased BV/TV when compared to DXR treatment (p<0.04). The trabecular number (Tb.N) decreased with DXR and DOX+DXR and increased with DOX+AMF treatments. This information will be useful in designing better cancer combination therapies that do not lead to vertebrae deterioration.
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Mwale et al. (2008) studied this question.
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