Protective Effects of 7-Hydroxycoumarin on Dyslipidemia and Cardiac Hypertrophy in Isoproterenol-Induced Myocardial Infarction in Rats.

This study evaluates the protective effects of 7-hydroxycoumarin (7-HC) on dyslipidemia and cardiac hypertrophy in isoproterenol (ISO) induced myocardial infarction (MI) in rats. Rats were pre- and co treated with 7-HC (16 mg/kg) daily for 8 days. ISO (100 mg/kg) was subcutaneously injected into rats on seventh and eighth days to induce MI. Increased activity/levels of serum creatine kinase-MB (CK-MB), troponin-T, plasma lipid peroxidation products, and altered levels of lipids in the serum and heart and serum lipoproteins were noted in ISO-induced rats. ISO-induced myocardial infarcted rats revealed increased hypertrophy (cardiac and left ventricular) and hepatic 3-hydroxyl 3-methylglutaryl-coenzyme-A reductase (HMG-CoA reductase) activity. Pre and cotreatment with 7-HC revealed significant protective effects on all the biochemical parameters evaluated. The in vitro study demonstrated its free radical scavenging property. Thus, 7-HC protects ISO-induced MI in rats by its free radical scavenging and antihyperlipidaemic and antihypertrophic properties.

Activation of ß1-adrenoceptor triggers oxidative stress mediated myocardial membrane destabilization in isoproterenol induced myocardial infarcted rats: 7-hydroxycoumarin and its counter action.

Activation of ß1-adrenoceptor stimulates myocardial membrane destabilization in isoproterenol induced rats. Male albino Wistar rats were pre and co-treated with 7-hydroxycoumarin (16mg/kg body weight) daily for 8 days. Myocardial infarction was induced into rats by the subcutaneous administration of isoproterenol (100mg/kg body weight) at an interval of 24h daily for a period of two days (7th and 8th day). The levels/activities of serum cardiac troponin-T, lactate dehydrogenase and the concentrations of heart lipid peroxidation products were significantly increased and the antioxidant status was significantly decreased in isoproterenol induced rats. Furthermore, the activity of sodium/potassium-dependent adenosine triphosphatase was significantly decreased and the activities of calcium and magnesium-dependent adenosine triphosphatases were significantly increased in the heart of isoproterenol induced myocardial infarcted rats. Isoproterenol induced rats also revealed increased concentrations of sodium and calcium and decreased concentrations of potassium in the heart. 7-hydroxycoumarin pre- and co-treatment showed considerable impact on all biochemical parameters assessed. Also, 7-HC greatly reduced the infarct size of the myocardium. The in vitro study confirmed its potent free radical scavenging activity. Thus, the present study revealed that 7-HC attenuates myocardial membrane destabilization by reinstating the activities/levels of adenosine triphosphatases and minerals in isoproterenol induced rats by inhibiting oxidative stress. These effects are attributed to the membrane stabilizing and free radical scavenging properties of 7-hydroxycoumarin.

Thymol attenuates inflammation in isoproterenol induced myocardial infarcted rats by inhibiting the release of lysosomal enzymes and downregulating the expressions of proinflammatory cytokines.

Inflammation plays an important role in the development of myocardial infarction (MI). The current study dealt with the protective effects of thymol on inflammation in isoproterenol (ISO) induced myocardial infarcted rats. Male albino Wistar rats were pre and co-treated with thymol (7.5mg/kg body weight) daily for 7 days. ISO (100mg/kg body weight) was injected subcutaneously into rats at an interval of 24h for two days (6th and 7th day) to induce MI. ISO induced myocardial infarcted rats showed increased levels of serum cardiac troponin-T, high sensitive C-reactive protein (hsCRP), lysosomal thiobarbituric acid reactive substances (TBARS) and elevated ST-segments. Also, the activities of lysosomal enzymes such as ß-glucuronidase, ß-galactosidase, cathepsin-B and D, the stimulators of inflammatory mediators were increased in the serum and heart of ISO induced myocardial infarcted rats. Furthermore, ISO up regulates the expressions of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) genes in the myocardium of rats analyzed by reverse transcription polymerase chain reaction (RT-PCR). Pre and co-treatment with thymol (7.5mg/kg body weight) near normalized the levels of lysosomal TBARS, activities of serum and heart lysosomal enzymes and downregulates the expressions of pro-inflammatory cytokines in the myocardium of ISO induced myocardial infarcted rats. Histopathological and transmission electron microscopic findings were also found in line with biochemical findings. Thus, the results of our study revealed that thymol attenuates inflammation by inhibiting the release of lysosomal enzymes and downregulates the expressions of pro-inflammatory cytokines by its potent anti-inflammatory effect.