Cardioprotective activity of flax lignan concentrate extracted from seeds of Linum usitatissimum in isoprenalin induced myocardial necrosis rats
Cardioprotective activity of flax lignan concentrate extracted from seeds of Linum usitatissimum in isoprenalin induced myocardial necrosis rats
Year: 2011
Authors: Zanwar, A.A. Hedge, M.V. Bodhankar, S.L.
Publication Name: Interdiscip. Toxicol.
Publication Details: Volume 4; Number 2; Pages 90 – 97.
Abstract:
The objective of the study was to evaluate the cardioprotective activity of flax lignan concentrate (FLC) in isoprenalin (ISO) induced cardiotoxicity in rats. Male Wistar rats (200�230 g) were divided into three groups. Group I: control, Group II: isoprenalin, Group III: FLC (500 mg/kg, p.o.) orally for 8 days and in group II and III isoprenalin 5.25 mg/kg, s.c. on day 9 and 8.5 mg/kg on day 10. On day 10 estimation of marker enzymes in serum and haemodynamic parameters were recorded. Animals were sacrificed, histology of heart was performed. Isoprenalin showed cardiotoxicity, manifested by increased levels of marker enzymes and increased heart rate. FLC treatment reversed these biochemical changes significantly compared with ISO group. The cardiotoxic effect of isoprenalin was less in FLC pretreated animals, which was confirmed in histopathological alterations. Haemodynamic, biochemical alteration and histopathological results suggest a cardioprotective protective effect of FLC in isoprenalin induced cardiotoxicity. (Authors abstract)
The pathophysiology of cellular damage due to heart disease related ischaemia is complex. Ischaemic tissue generates oxygen-derived free radicals which cause oxidative damage of membrane lipids, proteins and carbohydrates leading to qualitative and quantitative alterations of the myocardium. Isoprenalin (ISO), a synthetic catecholamine and β-adrenergic agonist is documented to produce myocardial infarction due to generation of highly cytotoxic free radicals through its auto-oxidation. Within 6 min of intraperitoneal isoprenalin injection, histological changes occur, including myofilament fragmentation. Flaxseed contains secoisolariciresinol diglucoside (SDG) which is converted by bacteria in the colon of humans and other animals to enterodiol and enterolactone, referred to as mammalian lignans. These exhibit weak estrogenic activity as they can bind to estrogen receptors on cell membranes. The objective of the present investigation was to study the effect of flax lignan concentrate (FLC) on isoprenalin induced cardiotoxicity in Wistar rats. In the present investigation, the observed changes in haemodynamic parameters after administration of isoprenalin significantly increased the HR compared to that of the control group. Increased myocardial oxygen demand leads to ischaemic necrosis of the myocardium in rats. ISO+FLC produced a non significant decrease in HR compared to that of ISO. After isoprenalin treatment, 24-h blood pressure measurement showed a non-significant decrease in MABP. FLC pretreatment attenuated the hypotensive effect of isoprenalin and tachycardia. In the isoprenalin group a significant increase in the enzyme CK-MB was noted indicating myocyte injury. A lesser increase in CK-MB after isoprenalin in the FLC-treated group indicated cardioprotective activity of FLC. The experimental data showed lowered activities of these enzymes in FLC-treated rats than in isoprenalin-treated rats, indicating protection against necrotic damage of the myocardial membrane. The lower LDH level in FLC-treated group, although is not significant, following isoprenalin insult, further supports the protective effect. Increase in the serum level of AST in the isoprenalin alone group compared to the control group indicates myocardial necrosis. FLC-treated rats had a lower level of AST, indicating cardioprotection. The activity of FLC also seems to preserve the structural and functional integrity of the myocardial membrane, as evident from the reduction in the elevated levels of these serum marker enzymes in rats pretreated with FLC when compared to the ISO alone group. Further, the data support the link between free radicals and cardiovascular tissue injury, associated mainly with increase in vascular ROS production. FLC exhibits antioxidant properties as a scavenger of different free radicals. The authors conclude that 10-day administration of FLC reduced isoprenalin-induced tachycardia. Protection from cardiotoxic effect of isoprenalin in FLC-pretreated animals was established by haemodynamic, biochemical, and histopathological results. The antioxidant effect appears to contribute to the cardioprotective effect of flax lignin concentrate in isoprenalin-induced cardiotoxicity. (Editors comments)
The pathophysiology of cellular damage due to heart disease related ischaemia is complex. Ischaemic tissue generates oxygen-derived free radicals which cause oxidative damage of membrane lipids, proteins and carbohydrates leading to qualitative and quantitative alterations of the myocardium. Isoprenalin (ISO), a synthetic catecholamine and β-adrenergic agonist is documented to produce myocardial infarction due to generation of highly cytotoxic free radicals through its auto-oxidation. Within 6 min of intraperitoneal isoprenalin injection, histological changes occur, including myofilament fragmentation. Flaxseed contains secoisolariciresinol diglucoside (SDG) which is converted by bacteria in the colon of humans and other animals to enterodiol and enterolactone, referred to as mammalian lignans. These exhibit weak estrogenic activity as they can bind to estrogen receptors on cell membranes. The objective of the present investigation was to study the effect of flax lignan concentrate (FLC) on isoprenalin induced cardiotoxicity in Wistar rats. In the present investigation, the observed changes in haemodynamic parameters after administration of isoprenalin significantly increased the HR compared to that of the control group. Increased myocardial oxygen demand leads to ischaemic necrosis of the myocardium in rats. ISO+FLC produced a non significant decrease in HR compared to that of ISO. After isoprenalin treatment, 24-h blood pressure measurement showed a non-significant decrease in MABP. FLC pretreatment attenuated the hypotensive effect of isoprenalin and tachycardia. In the isoprenalin group a significant increase in the enzyme CK-MB was noted indicating myocyte injury. A lesser increase in CK-MB after isoprenalin in the FLC-treated group indicated cardioprotective activity of FLC. The experimental data showed lowered activities of these enzymes in FLC-treated rats than in isoprenalin-treated rats, indicating protection against necrotic damage of the myocardial membrane. The lower LDH level in FLC-treated group, although is not significant, following isoprenalin insult, further supports the protective effect. Increase in the serum level of AST in the isoprenalin alone group compared to the control group indicates myocardial necrosis. FLC-treated rats had a lower level of AST, indicating cardioprotection. The activity of FLC also seems to preserve the structural and functional integrity of the myocardial membrane, as evident from the reduction in the elevated levels of these serum marker enzymes in rats pretreated with FLC when compared to the ISO alone group. Further, the data support the link between free radicals and cardiovascular tissue injury, associated mainly with increase in vascular ROS production. FLC exhibits antioxidant properties as a scavenger of different free radicals. The authors conclude that 10-day administration of FLC reduced isoprenalin-induced tachycardia. Protection from cardiotoxic effect of isoprenalin in FLC-pretreated animals was established by haemodynamic, biochemical, and histopathological results. The antioxidant effect appears to contribute to the cardioprotective effect of flax lignin concentrate in isoprenalin-induced cardiotoxicity. (Editors comments)
