Chitosan-Saponin-Bentonite Nanocomposites Prevent Doxorubicin-Induced Cardiovascular Toxicity by Inhibiting Oxidative Stress and Apoptosis

Introduction: Cardiovascular Diseases (CVDs) are the predominant chronic illness among the aged population. One in five people died from CDV in 2022, with approximately 700000 people losing their lives to the condition. Chitosan-saponin-bentonite nanocomposites (CSB-NC ) exhibit antioxidant, anti-inflammatory effects, as well as anti-proliferative and anti-apoptotic properties. The present study aims to examine the cardioprotective effects of CSB-NC against the cardiovascular toxicity associated with doxorubicin (Dox). Methods: Cardiovascular toxicity was induced in rats following the administration of Dox (3 mg/kg body weight, i.p.) on days 2, 4, 6, 8, 10, and 12. Thirty-six rats were divided into six groups, each consisting of six rats. The groups included: control, Dox, Dox + chitosan (60 mg/kg, orally), Dox + bentonite (60 mg/kg, orally), Dox + saponins (60 mg/kg, orally), and Dox + CSB-NC (60 mg/kg, orally). Results: Following CSB-NC treatment, the ST segment of the ECG exhibited partial normalization. CSB-NC reduced the levels of cardiac troponin T, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, malondialdehyde, nitric oxide, DNA fragmentation, and caspase-3, while it elevated glutathione, reduced catalase, nuclear factor erythroid 2–related factor 2 (Nrf2) expression, and Bcell leukemia/lymphoma 2 (Bcl-2). The CSB-NC-treated group exhibited a normal histological structure of cardiac muscle. Discussion: CSB-NC demonstrated a protective effect on the heart against Dox toxicity by enhancing the Nrf2 pathway, supporting the internal antioxidant system, and inhibiting the apoptotic pathway by reducing caspase-3 and stimulating Bcl-2 expression. Conclusion: CSB-NC showed a synergistic protective effect against cardiovascular toxicity induced by Dox when combined with saponin, chitosan, and bentonite.