Effect of Fraxetin on Oxidative Damage Caused by Isoproterenol-Induced Myocardial Infarction in Rats.

At present, cardiovascular disorders are the most prominent factors for the high morbidity rate globally. The occurrence of myocardial infarction followed by myocardial ischemia is the important cause of high death rates. Various medical treatments are available, yet the mortality and morbidity rate is high. In the present investigation, the cardioprotective property of fraxetin (Fx) is evaluated in myocardial infarction-induced experimental rats. Fraxetin, a phytochemical known as coumarin isolated from Fraxinus rhynchophylla. Fraxetin has numerous pharmacological activities including antioxidant, apoptosis inhibitor, anti-inflammatory, and antimicrobial agent. The experimental mice were split into 4 groups each comprising six animals. Group I was considered the control group; 0.1% NaCl solution was given as dosage. Group II received only Fx; group III was treated with ISO. Group IV was treated with Fx followed by ISO to induce myocardial infarction. In ISO administrated rats, there were changes in the heart weight, activities of cardiac markers, transmembrane protein activity, antioxidant enzymes, pro-inflammatory proteins, lipid profile, and myocardial structures. Pre-treatment of fraxetin in group IV experimental rats resulted in decreased cardiac weight, diminished level of cardiac markers (cardiac troponin T (cTnT), creatine kinase, creatine kinase-MB, and cardiac troponin I (cTnI)), reduced level of oxidative stress biomarkers (LOOH and TBARS) in the plasma and cardiac tissue, amplified level of enzymes in antioxidant defense system (catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPx)) in the plasma and heart tissue, and elevated level of ATPase activities. The histopathological studies also revealed the potent activity of fraxetin in protecting the cardiac tissues from inflammation and damage. ISO-administrated experimental rats treated with fraxetin exhibit increased antioxidants activity and decreased free radicals. Our study revealed that the administration of fraxetin significantly reduced the extent of myocardial damage during myocardial infarction in rats caused by isoproterenol. Thus, the results prove the cardioprotective effect of fraxetin in MI-induced rats.

Novel thiazole-pyrazolone hybrids as potent ACE inhibitors and their cardioprotective effect on isoproterenol-induced myocardial infarction.

A facile synthesis of a group of novel thiazole-pyrazolone hybrids and their investigation for angiotensin-converting enzyme (ACE) inhibition are reported in this study. These compounds were synthesized using a well-known approach, based on the condensation of ethyl acetoacetate with thiazolylhydrazines, and characterized by various spectroscopic and analytical techniques. The entire set of compounds displayed a moderate-to-excellent inhibitory activity against ACE. In particular, compound 4i was found to be the most potent ACE inhibitor and was further studied for cardioprotective effects against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Compound 4i improved the cardiac function and prevented cardiac injury induced by ISO in Sprague Dawley rats. The levels of oxidative stress and proinflammatory cytokines were also restored to near normal by 4i as compared with the ISO group. In the Western blot analysis, compound 4i prevented mitochondrial apoptosis after MI by downregulating the expression of cleaved caspase-3 and Bax, with the upregulation of Bcl-2, as compared with the ISO group.

[Role of endothelin-1 and its receptors on hypertrophy or proliferation of cultured cardial cells].

OBJECTIVE: To investigate the role of endothelin-1 and its receptors on hypertrophy or proliferation of cultured cardial cells. METHODS: Cardiomyocytes and cardiac fibroblasts were isolated by trypsin digestion method, DNA and protein synthesis were measured by 3H-dexyribonucleotidethymine (3H-TdR) and 3H-Leucine (3H-Leu) incorporation, while protein content was measured by Bradford method. Atrial natriuretic peptide (ANP) mRNA expression of cardiomyocyte was measured by reverse transcripted-polymerase chain reaction. Selective endothelin (ET) receptor subtype antagonists BQ123 and BQ788 were used to block ET(A) receptors (ET(A)R) and ET(B)R respectively and to observe the effects of the two receptors during cardiac hypertrophy. RESULTS: ET-1 significantly increased the 3H-TdR and 3H-Leu incorporation rate of cardiomyocytes and cardiac fibroblasts in a dose-dependent manner and increased protein content. Furthermore, ET-1 promoted the ANP mRNA expression of cardiomyocyte. ET(A)R antagonist remarkably blocked these effects, while ET(B)R antagonist had no obvious effect. CONCLUSIONS: ET-1 can induce the hypertrophy for cardiomyocytes and the proliferation for cardiac fibroblasts. These effects are mediated by ET(A)R.