Protective Effect of Silymarin Against Paclitaxel‐Induced Cardiotoxicity

Paclitaxel, a widely used chemotherapeutic agent, is known for its efficacy against various cancers but is also associated with significant cardiotoxicity. This study aimed to explore the potential of silymarin in mitigating Paclitaxel-induced cardiotoxicity in rats. To establish a model of Paclitaxel-induced cardiotoxicity, rats were injected intraperitoneally with Paclitaxel at 2 mg/kg for five consecutive days. Additionally, starting from day 6, silymarin was administered orally at a dose of 200 mg/kg for 10 days. Our findings indicate that silymarin reduced malondialdehyde (MDA) levels and increased the levels of antioxidant enzymes (SOD, CAT, GPx, and GSH) in heart tissue. Additionally, silymarin reduced serum cytokine levels (IL-1β, TNF-α, and IL-6) and improved serum lipid profiles, reducing lactate dehydrogenase (LDH), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and total cholesterol levels. Histopathological analysis revealed reduced inflammatory reaction scores in heart tissues. Immunohistochemical analysis revealed decreased PI3 kinase p85α scores, and western blot analysis showed downregulation of P2X7R, Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), and nuclear factor kappa B p65 (NF-κB-p65) expression. Silymarin also reduced Caspase-3 levels while increasing Bcl-2 protein expression, an antiapoptotic protein. These results suggest that silymarin has significant therapeutic potential for reducing Paclitaxel-induced cardiotoxicity via its antioxidant, anti-inflammatory, and anti-apoptotic properties.