Effects of menadione on the cardiovascular system
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M J Melgar1, A Anadon, J Bello
1Department of Toxicology, Faculty of Veterinary Medicine, University of Santiage de Compostela, Lugo, Spain.
Abstract:
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.
Insights
Menadione, a quinone, induced mild myocardial damage in rats, less severe than anthracyclines. This study investigated its effects on heart function and red blood cells, revealing subtle cellular changes.
Area of Science:
- Cardiology
- Toxicology
- Biochemistry
Background:
- Anthracycline cardiotoxicity mechanisms remain unclear, with free radical formation hypothesized.
- The quinone moiety of molecules like menadione is implicated in cellular damage.
Purpose of the Study:
- To investigate the effects of menadione on rat myocardial structure and function.
- To assess the impact of menadione on red blood cells and overall organ health.
Main Methods:
- Rats received escalating oral doses of menadione over 6 weeks.
- Evaluations included ECG, blood pressure, blood cell counts, and histopathological examination of heart, spleen, liver, and kidney.
- Myocardial ultrastructure was analyzed via electron microscopy.
Main Results:
- Menadione did not affect rat growth or cause significant ECG changes, though wave amplitude varied.
- Minor alterations in blood pressure were noted, with no significant hematological changes.
- Myocardial tissue showed subtle damage, including myofibril disorganization and mitochondrial changes, less severe than anthracycline-induced injury.
Conclusions:
- Menadione exhibits cardiotoxic potential, inducing observable myocardial damage.
- The observed damage is less pronounced compared to that caused by anthracyclines.
- Further research into quinone-induced cardiotoxicity is warranted.