Silymarin Decreases The Expression Of Vegf-A, Inos And Caspase-3 And Preserves The Ultrastructure Of Cardiac Cells In Doxorubicin Induced Cardiotoxicity In Rats: A Possible Protective Role

Doxorubicin (DOX) is the most effective and frequently used anticancer drug. This work aimed to study the protective role of silymarin (SIL) against DOX induced cardiotoxicity. Forty adult male rats were divided into four equal groups; Control, SIL, DOX and SIL-DOX treated groups. Control and SIL groups received daily oral saline (1 ml/kg) and SIL (60 mg/kg), respectively. DOX group received intraperitoneal (IP) injection of 1.66 mg/kg of DOX every second day. SIL-DOX group received the same mentioned doses of both drugs for 12 days. At the end of experiment, blood samples were collected for estimation of serum lactic dehydrogenase (LDH), Creatine phosphokinase (CPK) and aspartate transaminase (AST). Reduced glutathione (GSH) was also estimated. Cardiac specimens were processed for histological, immunohistochemical staining for detection of vascular endothelial growth factor A (VEGF-A), inducible nitric oxid synthase (iNOS), caspase-3 and ultra-structural study. Area percentages of collagen fibers, VEGF, iNOS and caspase-3 immuno expression were measured followed by statistical analysis. Control and SIL groups showed no changes. DOX group showed loss of myofibrils, hemorrhage and congested blood vessels. A highly significant increase in mean area percentage of collagen fibers (23.70 +/- 0.44), VEGF-A (27.76 +/- 0.57), iNOS (24.002 +/- 0.53) and caspase-3 (23.28 +/- 0.53) immunoexpression were also detected in DOX group. Mean concentration LDH (326.20 +/- 9.908), CPK (233.90 +/- 4.581) and AST (97.30 +/- 3.112) were increased, whereas GSH was decreased (2.23 +/- 0.157). Ultrastructural results revealed loss of myofibrils and intercalated discs and mitochondrial degeneration. These changes were improved in SIL-DOX group. It appears that SIL can protect against DOX-induced cardiotoxicity therefore, could be used in combination with doxorubicin in anticancer therapy.