The evaluation of rat peripheral blood morphology after coadministration of doxorubicin and tirapazamine
Keywords:
doxorubicin, tirapazamine, blood toxicityAbstract
Some cancer cells are typically characterized by hypoxia which is more resistant to radiotherapy and most common anticancer drugs. These specific phenomena encouraged researchers to the investigate new hypoxic-cell-selective cytotoxins. Tirapazamine (TPZ) is a representative of the drug-candidates group which demonstrates a considerable higher cytotoxic effect against hypoxic and then normoxic tumor cells studied under the same conditions. Taking into account that solid tumor does not only consist of hypoxic but also normoxic cells, a rational therapy should combine administration of classical anticancer therapy and TPZ. Results of some studies conducted under laboratory conditions indicated some benefits of such a schedule. Because doxorubicin (DOX), a widely used chemotherapeutic drug, has a similar mechanism of action as TPZ, we tested the hypothesis assuming interaction of both compounds in rats referring to blood toxicity. In this study we evaluated peripheral blood automatic smear in rats repeatedly treated with both DOX and TPZ. The major findings are that TPZ may statistically significantly change the relative amount of lymphocytes, MPV MCV and RDW in rats treated with DOX. Collectively, these findings suggest interactions between TPZ and DOX in relation to some red cells, white cells and platelets parameters, but the clinical risk of this phenomenon seems to be acceptable during chemotherapy. However, future studies are needed to assess the importance of anisocytosis as a result DOX-TPZ interaction.
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