A STUDY OF THE TOXIC EFFECT OF ADRIAMYCIN ON THE HEART OF ADULT MALE ALBINO RAT AND THE POSSIBLE PROTECTIVE ROLE OF PROBUCOL. HISTOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY
Hanan N. Gadallah, Tarek A. El-Ghamrawy and Mary A. Morcos
Department of Anatomy and Histology, Faculty of Medicine, Cairo University
Background: Adriamycin (ADR) has a broad spectrum of therapeutic activity against various tumors. However, the clinical use of ADR has been limited, due to its undesirable systemic toxicity especially on the heart. Many studies had been focused on the cardiomyocyte changes; however cardiac dilatation that occurs during prolonged ADR therapy implies effects on the extracellular matrix proteins. Aim of the work: The present work was desinged to determine the effects of ADR on the cardiomyocytes and extracellular matrix and the possible protective effects of probucol which is a lipid lowering drug with a strong antioxidant property. Material and Methods: Thirty six male albino rats were used in this study. They were divided into four groups. Group 1: control group, Group ІІ: rats given probucol, Group ІІІ: rats given ADR and Group ІV: rats were given ADR and probucol. Hearts were excised, processed and examined for light microscopic and immunohistochemical staining with anti- fibronectin which is an extracellular matrix protein. Also semithin sections were prepared. Results: Light microscopic examination of group III showed subendocardrial and focal damage of the myocardial cells characterized by myocytolysis and vacuolation. The affected fibres appeared pale and lacked cross striations due to myofibrillar loss. The interstitium showed lymphocytic infiltration, congestion of the blood capillaries and increased collagen deposition in the widened intercellular spaces. There was initial decrease of fibronectin expression followed by progressive increase of its expression in the extracellular matrix inbetween the cardiac myocytes. Examination of cardiac tissue in group IV displayed improvement of the histological changes as Probucol reduced the myocardial cell damage and fibrosis and fibronectin expression. Conclusion: probucol provided a partial protection against ADR induced cardiomyopathy which may be related to its antioxidant and lipid lowering properties. The increased expression of the extracellular protein fibronectin suggested its involvement in cardiac repair.