Resveratrol pre- and post-treatment in doxorubicin-induced cardiac injury in relation to endogenous stem cell activation

Abstract

Background: Doxorubicin (DOX), is a highly efficient anti-neoplastic drug used for treatment of solid tumors includingbreast cancer (BC). Resveratrol (RES) is considered an interesting molecule in hormone dependent cancer therapy. Stem cell activation may induce less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. Materials and Methods: Twenty seven adult male albino rats, were divided into: control group including 6 rats, group II (DOX group) including 7 rats that received intraperitoneal (IP) injection with DOX 3 mg /kg 3 times a week for 2 weeks. Group III (RES post-treatment group) included 7 rats that were injected with DOX followed by 50 mg/Kg RES daily orally for another 2 weeks. Group IV (RES pretreatment group) included 7 rats that were injected with DOX and received concomitantly 50 mg/Kg RES daily orally for 2 weeks and left untreated for another 2 weeks. By the end of the 4th week all animals were sacrificed. Cardiac muscle specimens were subjected to histological, immunohistochemical, morphometric and serological studies. Results: Myocardial injury appeared as obvious congestion, apoptosis, degeneration, increased collagen fibers content,obvious caspase3 expression and minimal proliferating cell nuclear antigen (PCNA) +ve and CD44 +ve expression in DOX group. Regression of the previous changes was more remarkable in group IV than in group III except for PCNA and CD44 expression that was more obvious in both treatment groups.Conclusion: RES proved amelioration of DOX induced myocardial injury that was more noticeable in RES early administration. RES post-treatment might have been more efficient if longer duration was applied.