Role of Matrix Metalloproteinase-2 in the Development of Cyclophosphamide-Induced Cardiomyopathy

Abstract

Immunohistochemical assay was employed to determine localization of MMP-2 in cardiomyocytes of WAG rats and changes in MMP-2 expression during modeled cardiomyopathy induced by single intraperitoneal injection of cyclophosphamide (125 mg/kg) alone or in combination with preventive intraperitoneal administration of an equal dose of asparcam-L (potassium-magnesium asparaginate) 30 min prior to the cytostatic. In the myocardium of control and experimental rats, MMP-2 was mostly located in cardiomyocyte nuclei. During the development of cyclophosphamide-induced cardiomyopathy (in 3 days after injection), the index of MMP-2-positive cardiomyocyte nuclei increased by 76%. In contrast to control hearts, MMP-2 was also expressed in the cardiomyocyte sarcoplasm. Preventive injection of asparcam-L moderated the cardiotoxic effect of cyclophosphamide, which manifested in less pronounced increase in the volume density of cardiomyocytes with lytic changes (by 42%) and index of MMP-2⁺ cardiomyocyte nuclei (by 23%) in comparison with the rats exposed to cyclophosphamide alone.