Effect of doxorubicin on dystrophin‐glycoprotein complex and its correlation with cardiac function loss in rats

Doxorubicin (DOX) is associated with dose‐dependent cardiomyopathy and, the cardiac changes could be attributed to alterations in the dystrophin‐glycoprotein complex (DGC). The importance of the DGC in maintaining sarcolemmal stability led us to hypothesize that loss of the DGC components could be involved in DOX‐cardiomyopathy and has been suggested as a common pathway for contractile dysfunction. Rats received cumulative doses of DOX: 3.75, 7.5 and 15mg/kg. Controls received saline. At 14 days after the last injection, the hearts were collected for immunofluorescence (IF) and Western blot (WB). The cardiac function was evaluated using echocardiography. Dose‐dependent downregulation of dystrophin and β‐dystroglycan expression using IF and WB were observed in DOX‐treated hearts. Consonantly, detection of positive albumin‐stained cardiac muscle cells with disrupted dystrophin pattern and preserved plasma membrane integrity was consistent with increased sarcolemmal permeability. Dose‐dependent impairment of ejection fraction was also observed in DOX‐treated rats. Our data provide novel insight regarding DGC disruption in experimental DOX‐cardiomyopathy. Significant decrease of dystrophin and dystroglycan may result in loss of sarcolemmal permeability that might play an important role in cardiomyocyte damage in DOX‐cardiomyopathy with impairment of cardiac function. Supported by Fapesp.