Oxidative stress induced cardiomyocytes injury by Tamoxifen and abrogates by zinc supplement in adult female rabbits

Abstract

Tamoxifen (TAM) is used in breast cancer chemotherapy since its approval by the Food and  Drug Administration in 1977. However, TAM therapy is accompanied with cardiomyocytes apoptosis. Oxidative stress and inflammation are the major implicated mechanisms contributing to TAM apoptosis. In this study, we explored whether zinc (Zn) supplementation could prevent TAM-induced cardiomyocytes injury in adult female rabbits. Rabbits were received zinc orally (0.3 mg/ kg body weight / day for 42 days) in zinc group, Tamoxifen group were received orally (0.25 mg/ kg body weight for 42 days), and combination (Zn+Tam) group were received equal dose from zinc and tamoxifen. To study the effect of the tamoxifen (selective estrogen receptor modulator) on the cardiac muscle. Results showed of histopathological study of heart taken from zinc treated group not showed any important abnormalities in histological appearance, tamoxifen group in heart tissue showed a massive necrotic tissue  and a huge inflammatory cell infiltration to damaged area and combination group lesion showed active inflammatory process which included blood vessels congestion, edema formation,  inflammatory cell aggregation especially macrophage and Myocyte vacuolization. As a consequence, the finding of the research Tam induction over production of reactive oxygen species (ROS) within cardiac cell and the imbalance between the ROS generating system and the antioxidant system can lead to a potentially harmful to tissues and cells.