A low dose of doxorubicin improves antioxidant defence system and modulates anaerobic metabolism during the development of lymphoma

Abstract

Objective:The objective of the present study is to find low dose of doxorubicin (DOX) with cancer preventive activity and to check the implication of this low dose of DOX on antioxidant defence system during lymphoma growth in mice, as the clinical utility of anthracycline anticancer drugs, especially DOX is limited by a progressive cardiotoxicity linked to mitochondrial damage.Materials and Methods:We selected a dose of DOX (0.90 mg/kg body weight of mouse), which is about 20 folds lower than clinically used dose for cancer treatment. The cancer preventive action is monitored by modulation of anaerobic metabolism. The effect of this dose on antioxidant defence system is analyzed by testing the activities of antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST). The activities of these enzymes were monitored at different intervals during the growth of lymphoma in mice.Results:The activities of antioxidant enzymes, such as CAT, SOD, and GST, were found to decrease gradually during the growth of lymphoma in mice. The anaerobic metabolism was increasing with lymphoma growth. We report that about 20 folds lower dose of DOX enhances the activities of antioxidant enzymes and decreases anaerobic metabolism during the development of lymphoma. These enzymes of antioxidant defence system suppress oxidative stress and mitochondrial damage, whereas a decrease in anaerobic metabolism checks cancer growth.Conclusions:The result suggests that dose cumulative cellular toxicity of DOX may be avoided by treating cancer in animals with lower doses of DOX in combination with other drugs.