Curcumin Ameliorates Doxorubicin-Induced Cardiotoxicity and Hepatotoxicity Via Suppressing Oxidative Stress and Modulating iNOS, NF-κB, and TNF-α in Rats

Doxorubicin (DOX) is one of the widely used anti-tumor drugs. However, DOX-induced cardiotoxicity (DIC) and hepatotoxicity (DIH) are among the side effects that limited its therapeutic efficiency and clinical applicability. This study aimed to investigate the cardioprotective and hepatoprotective potentials of curcumin (CMN)-a bioactive polyphenolic compound-in alleviating DOX-induced cardiotoxicity (DIC) and hepatotoxicity (DIH) in male rats. A single intraperitoneal (i.p.) dose of DOX (20 mg/kg) was used to induce DIC and DIH. DOX-intoxicated rats were co-treated with CMN (100 mg/ kg, oral) for 10 days before and 5 days after a single dose of DOX. We studied the anti-inflammatory and anti-oxidative activities of CMN on biochemical and immunohistochemical aspects. DOX disrupted cardiac and hepatic functions and stimulated oxidative stress and inflammation in both tissues that was confirmed biochemically and immunohistochemically. DOX enhanced inflammatory interferon-gamma (IFN-gamma) and upregulated immunoexpression of nuclear factor-kappa B (NF-kappa B), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-alpha). DOX induced structural alterations in both cardiac and hepatic tissues. CMN demonstrated cardioprotective potential through reducing cardiac troponin I (cTn1) and aspartate amino transaminase (AST). In addition, CMN significantly ameliorated liver function through decreasing alanine amino transaminase (ALT) and, gamma-glutamyl transferase (GGT), total cholesterol (TC), and triglycerides (TG). CMN demonstrated anti-inflammatory potential through decreasing IFN-gamma levels and immunoexpression of iNOS, NF-kappa B, and TNF-alpha. Histopathologically, CMN restored DOX-associated cardiac and liver structural alterations. CMN showed antioxidative and anti-inflammatory potentials in both the cardiac and hepatic tissues. In addition, cTn1, IFN-gamma, and AST could be used as blood-based biomarkers.