ACUTE TOXICITY STUDY AND THERAPEUTIC ACTIVITY OF MODIFIED ARJUNARISHTA ON ISOPROTERENOL-INDUCED MYOCARDIAL INFARCTION IN RATS

Abstract

Objective: Ayurvedic formulation derived phytomedicine could bring a specific remedy against myocardial infarction (MI) without any side effects. Arjunarishta is a cardio tonic that nourishes and strengthens the myocardial muscle and promotes cardiac function. The preparation of Arjunarishta is modified and it does not involve fermentation. So it is alcohol-free and safe to all age groups. The study of acute toxicity and therapeutic activity of Modified Arjunarishta (MA) in isoproterenol (IPN) induced MI in rats was conducted to bring scientific evidence. Methods: Acute toxicity study: Mice are divided into three groups. Group I-control group; Group II and group III were test groups and they received an oral dose of 1000 mg/kg and 2000 mg/kg of MA, respectively. The experimental mice were observed for behaviour changes and clinical signs. Their body weight was also recorded. At the end of the experiment, blood sample was collected and glucose, liver function test (LFT), renal function test (RFT) and haematology parameters were analysed. Then they also subjected to gross pathological examination of all the major internal organs. Therapeutic study: Rats were divided into six groups. Group 1-normal control; Group 2 (induced)-IPN 85 mg/kg for the first two days; Group 3 (MA low dose)-received IPN as per group 2 followed by MA 200 mg/kg from the 3rd day to the end of the experiment; Group 4 (MA medium dose)-400 mg/kg; Group 5 (MA high dose)-600 mg/kg; Group 6 (Standard)-IPN as per group 2 followed by Arjunarishta 2 ml/kg body weight from the 3rd day to the end of the experiment. The collected serum sample was used for the estimation of myocardium-expressed proinflammatory cytokines. Heart tissue was homogenized for the estimation of calcium and lipid profile. Results: Acute toxicity: There were no signs of toxicity and no significant change in body weight. The value of glucose, RFT, LFT and haematological parameters are remained normal. Histopathological report showed normal architecture. Therapeutic activity: In the heart samples, significantly (p<0.001) increased cholesterol, Triglyceride (TGL), Free Fatty acids (FFA) and calcium in IPN induced groups was noted. They are all significantly (p<0.001) decreased in MA administrated groups of three different groups. In serum sample, a significantly (p<0.001) increased cytokines of Tumor necrosis factor α (TNFα), Interlukins (IL-6, IL-1α and IL-1β) in IPN induced rats was recorded were as they get significantly (p<0.001) decreased in MA administrated groups of three different doses. Conclusion: The results obtained from the acute toxicity experiment concluded that MA was found to be safe for oral administration. The therapeutic experiment results clearly emphasize the beneficial action of MA against IPN induced MI in rats.