CONTRIBUTION TO RESEARCH ON THE PROTECTIVE EFFECT OF PROANTHOCYANIDOL-BP1 ON ADRIAMYCIN-INDUCED CARDIOTOXICITY

The anthracycline antibiotic adriamycin (ADR) is among the most effect ive 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 numb er of cardioprotectors have been tested so far but only a few of them have shown significant cardioprotection without altering 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 treat ment. The aim of this study was to evaluate whether the administration of proanthocyanidol - BP1 to ADR -treated mice could diminish or prev ent ADR-cardiotoxicity. Mice were pretreated with BP1 (20 mg/kg ip) or saline 3 days before ADR treatment. On the fourth day of the experime nt 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 w ere evaluated 4 days after ADR treatment. No morphological changes wer e found in the hearts of mice receiving either BP1 or saline. In salin e pretreated mice receiving 15 mg/kg ADR multiple, single or small gro ups of cardiac myocytes with myofibrillar lysis were found widely spre ad throughout the myocardium. In saline pretreated mice receiving 20 m g/kg ADR necrotic areas of myocytes were found in the left ventricle. However, mice pretreated with BP1, regardless of the ADR dose, had les s pronounced histological changes. In 7 out of 8 mice in the ADR20BP1 group only a few single cardiac myocytes with myofibillar lysis were f ound. On the basis of the light microscopy evaluation of the hearts of ADR-treated mice it was noted that myofibrillar lysis was the prevale nt type of cardiac damage. In BP1-pretreated mice the degree of cardia c damage related to ADR toxicity was less intensive in comparison with unprotected mice. The results obtained suggest the need of further ev aluation of BP1 as a potentially cardioprotective compound.