The potential role of combined antioxidants against doxorubicin-induced toxicity in rats

Abstract

The therapeutic usefulness of doxorubicin (DOX) is limited by its cardiotoxicity. Many recent studies have shown that DOX toxicity involves generation of reactive oxygen species (ROS). This study was carried out to investigate the effects of combined antioxidants (vitamin E, 250 mg/kg b.wt/day, p.o + sodium selenite 0.5 mg/kg b.wt/day, p.o + turmeric 50 mg/kg b.wt/day, p.o) against doxorubicin induced toxicity in rats. Thirty six Sprague Dawely female rats were divided into six groups. Group A: control, saline (5ml/ Kg b.wt, p.o); Group B: toxic control for pretreatment, received single dose of DOX (8 mg/kg b.wt, i.p) and sacrificed after 48h; Group C: pretreatment, received antioxidants for seven days and on 5th day a single dose of DOX; Group D: Toxic control for post treatment, a single dose of DOX on the first day and sacrificed at 7th day; Group E: post treatment, received the antioxidants for seven days and on the first day a single dose of DOX and Group F: received antioxidants for seven days. Doxorubicin injection resulted in significant elevation in lipid peroxide level in plasma, heart and liver with a significant reduction in the activities of superoxide dismutase (Cu, Zn-SOD), in heart and liver, as well as reduced glutathione (GSH) levels in blood, heart and liver were reduced. These changes paralleled with significant elevation of liver enzymes activities such as alanine transaminase (ALT) and aspartate transaminase (AST); kidney function tests urea and creatinine and plasma lipids. Pre and post treatments of the combined antioxidants elicited effectiveness in counteracting these biochemical disturbances but the recorded values couldn’t attain those of the control group. Furthermore, pretreatment with the combined antioxidants attenuated DOX-induced toxicity more effectively than post treatment. In conclusion pre- and post treatment with combination of vitamin E, selenium and turmeric were effective in minimizing the toxic side effects of DOX, Suggesting that supplementation with these antioxidants could improve the therapeutic value of the drug.