Contribution to research on the protective effect of proanthocyanidol-BP1 on adriamycin-induced cardiotoxicity

Abstract

The anthracycline antibiotic adriamycin (ADR) is among the most effective drugs used for treatment of hematopoietic malignancies as well as for advanced solid malignant tumours. Unfortunately, ADR-dose-related cardiotoxicit limits the use of this drug in clinical practice. A number of cardioprotectors have been tested so far but only a few of them have shown significant cardioprotection without allering the clinical efficancy of ADR. There have been many demonstrations in animal models that natural antioxidant compounds, including flavanoids, diminsh or prevent both acute and chronic pathologic changes related to ADR treatment. The aim of this study was to evaluate whether the administration of proanthocyanidol - BP1 to ADR -treated mice could diminish or prevent ADR-cardiotoxicity. Mice were pretreated with BP1 (20mg/kg ip) or saline 3 days before ADR treatment. On the fourth day of the experiment ADR was given in a dose of 15 or 20 mg/kg ip 1h after BP1 or saline. Histological changes related to ADR toxicity in the left ventricle were evaluated 4 days after ADR treatment. No morphological changes were found in the hearts of mice receiving either BP1 or saline. In saline pretreated mice receiving 15 mg/kg ADR multiple, single or small groups of cardiac myocytes with myofibrillar lysis were found widely spread throughout the myocardium. In saline pretreated mice receiving 20 mg/kg ADR necrotic areas of myocytes were found in the left ventricle. However, mice pretreated with BP1, regardless of the ADR dose, had less pronounced histological changes. In 7 out of 8 mice in the ADR20BP1 group only a few single cardiac myocytes with myofibillar lysis were found. On the basis of the light microscopy evaluation of the hearts of ADR-treated mice it was noted that myofibrillar lysis was the prevalent type of cardiac damage. In BP1-pretreated mice the degree of cardiac damage related to ADR toxicity was less intensive in comparison with unprotected mice. The results obtained suggest the need of further evaluation of BP1 as a potentially cardioprotective compound.