Protective Effect Of Apigenin On Daunorubicin-induced Cardiotoxicity In Mice And Its Mechanisms

Objective:To examine the protective effect of apigenin on daunorubicin-induced cardiotoxicity and to probe into the possible mechanisms.Methods:Forty male Kunming mice were used and randomly divided into the control, model, apigenin 100 and 200 mg/kg groups. The mice in the medicine-treated groups were orally given apigenin 0.2 ml/10 g body weight by gavage based on different dose in the morning, and the control and model mice were orally given the same amount of 0.5% sodium carboxymethyl cellulose solution. All the mice were administered continuously for 8 days. On the eighth day after administration for 1 h, the mice in the model and apigenin-treated groups were given 30 mg/kg daunorubicin by intraperitoneal injection to induce the cardiotoxic model. All the mice were continued dosing for 2 days again. At 1 h after the last administration, all the mice were anesthetized with 3% chloral hydrate and the electrocardiographs were recorded. Then these mice were killed and blooded from the retinal venous plexus, the serums were separated. The serum lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) activities were determined according to the methods provided by the kits, respectively. The left ventricle samples were collected to make into pathological sections, and the histopathological changes of myocardium were evaluated under a light microscope. Meanwhile, appropriate amount of cardiac tissues were collected to prepare 10% homogenate with ice physiological saline, the myocardial reduced glutathione (GSH), glutathione reductase (GR), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD) and malondialdehyde (MDA) contents were determined according to the manufacturer’s instructions.Results:After pretreatment of mice with apigenin, the serum LDH, CK and AST activities were dose-dependently decreased, the arrhythmia incidence of mice was reduced, and the severity of myocardial injury was improved, especially in the apigenin 200 mg/kg group (P<0.05 or P<0.01). The myocardial MDA content in the apigenin-treated groups was decreased in different degrees, while the myocardial GR and GSH-Px activities were dose-dependently increased, especially in the apigenin 200 mg/kg group (P<0.05 or P<0.01). Compared with the model group, the myocardial GSH content in the apigenin-treated groups was decreased, especially in the apigenin 200 mg/kg group (P<0.01). The myocardial T-SOD and GST activities were no significant difference between the model and apigenin-treated groups.Conclusion:Apigenin may reduce the daunorubicin-induced cardiotoxicity, and the mechanisms may be related to the antioxidant group of its chemical structure and its antioxidation via the increments of myocardial GR and GSH-Px activities.