FORMONONETIN ATTENUATES ISOPROTERENOL-INDUCED CARDIAC TOXICITY IN RATS OWING TO ITS ANTI-OXIDANT, ANTI-INFLAMMATORY AND ANTI-APOPTOTIC ACTIVITY

Abstract

Objective: A high rate of mortality and morbidity is associated with myocardial infarction (MI), indicating a need to hunt for newer treatment modalities. Formononetin (FMN) is a dietary flavonoid with remarkable anti-oxidant and anti-apoptotic properties. Therefore, the aim of this study was to evaluate the ability of FMN in attenuating isoproterenol (ISO) induced oxidative stress and myocardial infarction. Design and method: A total of 48 Male Wistar rats were administered either FMN (5, 10 or 20 mg/kg/day, i.p.) or vehicle for 15 days along with subcutaneous ISO, 85 mg/kg for 2 consecutive days i.e. 13th and 14th days. On the 15th day, rats were anaesthetized followed by cannulation of right coronary artery to record hemodynamic parameters. Blood sample was collected and heart was excised to evaluate for biochemical, histopathological, ultrastructural and immuohistochemical studies. Results: ISO-treated rats demonstrated disturbed hemodynamic. There was also a significant decrease in antioxidant enzyme levels and increase in the level, of malondialdehyde, serum TNF-α and IL-6. The cardiac injury markers like creatine kinase-MB and lactate dehydrogenase were increased in the serum. Additionally, immunohistochemistry displayed an increased Bax/Bcl-2 ratio in the myocardium. Histopathological and ultrastructural studies support the protective effect of FMN in ISO- induced myocardial infarcted rats. Conclusions: FMN alleviates myocardial damage in ISO induced cardiac injury by preserving hemodynamic and biochemical function and reducing inflammation due to its anti-apoptotic, anti-inflammatory and antioxidant activities.