CARDIAC HEMODYNAMIC, FUNCTIONAL AND MORPHOLOGICAL EVALUTION OF SELECTED STRUCTURALLY-RELATED FLAVONOIDS IN FRUCTOSE-STREPTOZOTOCIN-INDUCED DIABETIC RATS

Abstract

Diabetes mellitus is a combination of heterogeneous disorders commonly presenting with episodes of hyperglycaemia and glucose intolerance, defective insulin action, or both. Diabetic cardiovascular disease (DCD) is a frequent complication of diabetes characterized by myocardial dysfunction due to hypertension, inflammation, myocardial fibrosis, myocardial apoptosis, mitochondrial damage and oxidative stress. In this study, cardiac hemodynamic, functional and histological effects of taxifolin (0.25 mg/kg, 0.5 mg/kg 1.0 mg/kg), eriodictyol (0.25 mg/kg, 0.5 mg/kg 1.0 mg/kg), rutin (5.0 mg/kg, 10.0 mg/kg and 20.0 mg/kg) and quercetin (5.0 mg/kg, 10.0 mg/kg and 20.0 mg/kg) in fructose-streptozotocin-induced diabetic rats were investigated. Type-II diabetes was induced in adult male Wistar rats by 14 days 10% fructose feeding ad libitum followed by administration of 40 mg/kg streptozotocin, interperitoneally. After 72 hours, animals with blood glucose level ≥250 mg/dl were selected and used for subsequent experiments. Animals were divided into normal control group, diabetic-control group and group of diabetic animals post-treated with graded doses of taxifolin, eriodictyol, rutin orquercetin. Measurements of hemodynamic parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), heart rate and ECG) were taken. Treatment with flavonoids lasted for 11 days and animals were sacrificed 24 hours after the last administration of the selected flavonoids. Measurement of hemodynamic parameters were repeated before sacrifice. After sacrifice, hearts were excised and blood samples collected and processed for biochemical estimations. Assays for oxidative stress markers (activities of catalase and superoxide dismutase, and reduced glutathione concentration), markers of inflammation(activities of myeloperoxidase and nitric oxide level), cardiac function biomarkers (creatinine kinase-MB, C-reactive protein) and cardiac troponin I, and glycated hemoglobin were carried out. Histopathological examination of the heart was carried out using Haematoxylin and Eosin staining (H&E). Results indicated that there was significant (p<0.0001) reduction of blood glucose and glycated haemoglobin level in diabetic treated rats when compared to the control group. Graded doses of the selected flavonoids significantly reduced oxidative stress (p<0.0001), cardiac function markers (p<0.0001), blood pressure (p<0.0001), electrolyte imbalance (p<0.0001), and improved lipid profiles (p<0.0001).There was significant (p<0.0001) correction of blood pressure parameters, a significant (p<0.0001) improvement of heart rate and electrocardiography measurements. The results also highlighted the influence of some structural feature on the bioactivity of the flavonoids Conclusively, taxifolin, eriodictyol, rutin and quercetin showed multi-mechanistic cardio-protective effects through antioxidant, anti-inflammatory, anti-myocardial infarction which makes them a promising therapeutic targets for the treatment of diabetic cardiovascular diseases.