Abstract

Cancer chemotherapy with doxorubicin, despite high antitumor activity and broad spectrum of this drug, is on decline due to toxic side effects. The clinical efficacy of anthracyclines have continuously prompted the search for new adjuvants to alleviate undesirable side toxicity incurred by this group of cytostatics. The recent approaches involve the application of synthetic or purified natural antioxidants in combination with doxorubicin following the observation that at least some side toxic effects, cardiotoxicity in particular, stem from stimulation of formation of reactive oxygen species by this drug. In contrast, our research represents a purely nutritional approach and is aimed at finding out whether special design of patients' diet, i.e. enrichment in a food item with high antioxidative potential, can influence the final outcome of cancer therapy.In the first series of experiments, we checked whether the proposed dietary intervention with beetroot juice might have any impact on therapeutic efficacy of doxorubicin. For this purpose, leukaemia L1210 bearing mice were treated with doxorubicin and fed beetroot juice ad libitum (instead of water) for 7 or 14 days. Control mice received water to drink. Doxorubicin was very effective in prolonging survival time of leukaemia bearing mice (ILS about 400%). However, only in groups receiving this drug in combination with beetroot juice total cures were observed. These were not sporadic events but concerned about 50% of animals. Moreover, in all mice groups drinking beetroot juice, the animals were more lively and displayed better appetite, as if they tolerated better both the disease and chemotherapy.In separate series of experiments, leukaemia L1210 bearing mice were fed beetroot juice ad libitum instead of water for 7 days and then were treated with doxorubicin applied in different schemes. From control and treated mice, bloods and hearts were collected and analysed for various markers of oxidative insult. In blood, the integrity of DNA in white blood cells has been determined by comet assay and the level of isoprostanes in plasma. In hearts, also by means of comet assay, DNA damage in cardiomyocytes was evaluated. The results revealed that although doxorubicin induced immediate extensive oxidation of lipids and DNA damage, especially in cardiac tissue, the dietary intervention with beetroot juice prior to doxorubicin treatment clearly decreased all markers of oxidative stress tested.

Authors (9)