title: Cardioprotective response to chronic administration of vitamin E in isoproterenol induced myocardial necrosis: Hemodynamic, biochemical and ultrastructural studies.
abstract: The present study evaluated the cardioprotective potential of vitamin-E by studying its effect on hemodynamic parameters, lipid peroxidation, myocyte injury marker and ultrastructural changes in model of isoproterenol-induced myocardial necrosis in rats. Wistar albino male rats (150-200 g) were randomly divided into saline, ISP control, and vit E groups. Vitamin E group was administered vitamin E at a dose of 100mg/kg/day while saline and ISP control groups received saline orally for one month. On 29(th) and 30(th) day, ISP (85 mg/kg, sc) was administered at an interval of 24 h to vit E and ISP control rats. On 31(st) day, rats of all groups were anesthetized and hemodynamic parameters were recorded. At the end of experimentation, animals were sacrificed; hearts were excised and processed for biochemical and ultrastructural studies. ISP administration produced marked cardiac necrosis as evidenced by significant decrease in my ocardial creatine kinase-MB as well as increase in malonaldialdehyde levels. ISP-induced myocardial necrosis resulted in myocardial dysfunction as evidenced by significant depression in heart rate and mean arterial pressure in the ISP control group as compared to saline control. Salient ultrastructural changes including extensive loss of myofibrils, muscle necrosis, loss of mitochondria, and formation of several intracytoplasmic vacuoles and lipid droplets further confirmed the ISP-induced myocardial damage. However, subsequent to ISP challenge, vit E treatment significantly preserved the myocardium by restoring myocardial CK-MB activity, inhibiting the ISP-induced lipid peroxidation and ultrastructural changes. Additionally, pre-and co-treatment of vit E prevented the deleterious ultrastructural changes caused by ISP. These beneficial effects of chronic vit E treatment also translated into significant restoration of the altered hemodynamic parameters. The present study clearly demonstrated the cardioprotective potential of vit E at dose of 100 mg/kg in ISP-induced model of myocardial necrosis in rats. The significant restoration of altered hemodynamic parameters, myocardial CK-MB activity, prevention of ISP-induced rise in lipid peroxidation and ultrastructural changes may confirm its cardioprotective effect.
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, 110029 New Delhi, India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Nandave
authors.forename: Ipseeta
authors.initials: I
authors.lastname: Mohanty
authors.forename: T C
authors.initials: TC
authors.lastname: Nag
authors.forename: Shreesh Kumar
authors.initials: SK
authors.lastname: Ojha
authors.forename: Rajan
authors.initials: R
authors.lastname: Mittal
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumari
authors.forename: Dharamvir Singh
authors.initials: DS
authors.lastname: Arya
keywords: Isoproterenol; Myocardial necrosis; Rats; Vitamin E