Effects of menadione on the cardiovascular system

Cardiotoxic mechanisms induced by anthracyclines are not clearly determined. A possible hypothesis is free radical formation and cell damage due to the quinone part of the molecule. We have studied the effect of menadione on myocardial structure and function. The effect on the red blood cells has been also determined. Groups of rats were treated orally with increasing doses (5 mg/kg/d, increased to 20 mg/kg/d and 40 mg/kg/d in the 3rd and 5th w, respectively). Duration of treatment was 6 w. ECG and blood pressure changes and blood cell count, including Heinz-Ehrlich bodies and reticulocytes, hemoglobin and hematocrit, were determined before and after treatment weekly and every 2 w, respectively. At the end of the experiment, the hearts of 2 rats/group were processed for electron microscopy. Heart, spleen and liver weights were determined. Heart, spleen, liver and kidney were subjected to histopathological examinations. Menadione treatment did not affect growth. No significant ECG changes were obtained; only significant changes of wave amplitude were observed. Menadione caused no relevant hematological changes but there were some blood pressure alterations. Morphological changes in myocardial tissue were observed including a small disorganization of myofibrils and mitochondria crystolisis. Z-lines appear forming zigzags. There were differences in organ weights. This study showed the damage induced by menadione was less than injury induced by anthracyclines.