Oxidative stress markers may not be early markers of doxorubicin-induced cardiotoxicity in rabbits

Abstract

This study was performed to determine whether oxidative stress markers may be early markers of doxorubicin-induced cardiotoxicity. Forty-four male rabbits were randomly divided into four doxorubicin groups and one control group (8 rabbits). The control group received saline, and rabbits in the doxorubicin groups received 2 mg/kg doxorubicin weekly for 1 (group 1, 8 rabbits), 2 (group 2, 8 rabbits), 4 (group 3, 9 rabbits) or 8 (group 4, 11 rabbits) weeks. Echocardiography was performed to measure left ventricular ejection fraction, fractional shortening and the E/A ratio. Cardiotoxicity scores were determined by light microscopy using Billingham's method and by electron microscopy. Serum glutathione peroxidase (GPx) and superoxide dismutase (SOD) concentrations were quantified by a rabbit-specific enzyme-linked immunosorbent assay (ELISA). The Billingham cardiomyopathy scores for the rabbits in groups 3 or 4 were significantly higher (p<0.05) compared to the scores for the control group or groups 1 and 2. Myocardial injury was demonstrable by electron microscopy in groups 2, 3 and 4 (p<0.05). Serum GPx concentrations decreased only in group 4 compared to the control group (p<0.05). No changes were measured in serum SOD concentration. The results indicate that oxidative stress markers may not be early markers of doxorubicin-induced cardiotoxicity.