A novel synthetised sulphonylhydrazone coumarin (E)-4-methyl-N'-(1-(3-oxo-3H-benzo[f]chromen-2- yl)ethylidene)benzenesulphonohydrazide protect against isoproterenol-induced myocardial infarction in rats by attenuating oxidative damage, biological changes and electrocardiogram.

Coumarins and their derivatives are becoming a potential source for new drug discovery due to their vast array of biological activities. The present study was designed to investigate the cardioprotective effects of a newly synthesised coumarin, symbolised as 5,6-PhSHC, against cardiac remodelling process in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats by evaluating haematological, biochemical and cardiac biomarkers. Rats were pre/co-treated with 5,6-PhSHC or clopidogrel (150 µg/kg body weight) daily for a period of 7 days and then MI was induced by injecting ISO (85 mg/kg body weight), at an interval of 24 hours for 2 consecutive days, on the sixth and seventh days. The in vivo exploration indicated that the injection of 5,6-PhSHC improved the electrocardiographic (ECG) pattern and prevented severe heart damage by reducing leakage of the cardiac injury markers, such as troponin-T (cTn-T), lactate dehydrogenase (LDH), and creatine kinase-MB. The cellular architecture of cardiac sections, altered in the myocardium of infracted rats, was reversed by 5,6-PhSHC treatment. Results showed that injection of 5,6-PhSHC elicited significant cardioprotective effects by prevention of myocardium cell necrosis and inflammatory cells infiltration, along with marked decrease in plasma levels of fibrinogen. In addition, the total cholesterol, triglyceride, LDL-c, and HDL profiles underwent remarkable beneficial changes. It was also interesting to note that 5,6-PhSHC enhanced the antioxidative defence mechanisms by increasing myocardial glutathione (GSH) level, superoxide dismutase (SOD), and catalase (CAT) activities, together with reducing the levels of thiobarbituric-acid-reactive substances (TBARS), when compared with ISO-induced rats. Taken together, these findings suggested a beneficial role for 5,6-PhSHC against ISO-induced MI in rats. Furthermore, in silico analysis showed that 5,6-PhSHC possess high computational affinities (E-value >-9.0 kcal/mol) against cyclooxygenase-2 (PDB-ID: 1CX2), vitamin K epoxide reductase (PDB-ID: 3KP9), glycoprotein-IIb/IIIa (PDB-ID: 2VDM) and catalase (PDB-ID: 1DGF). Therefore, the present study provided promising data that the newly synthesised coumarin can be useful in the design and synthesis of novel drug against myocardial infarction.

Toxic effect of alpha cypermethrin, an environmental pollutant, on myocardial tissue in male wistar rats.

α-Cypermethrin (CYP) is a pyrethroid insecticide-like environmental pollutant, widely found in the environment. New research links exposure to high levels of CYP to health damage; however, little is known about the effect of CYP on cardiovascular disease. The purpose of the present study was to evaluate, for the first time, biochemical and cardiovascular changes in male rats resulting from subchronic CYP exposure. The animals were divided into three groups: group 1 served as the control, group 2 (CYP1) received 4 mg/kg of CYP by gavage, and group 3 (CYP2) received 8 mg/kg of CYP by gavage, for 8 weeks each. Results showed that both CYP1 and CYP2 markedly increased plasma concentrations of cardiac markers (LDH, CK-MB, and troponin-T). Moreover, compared to the control group, CYP treatment elevated cardiac oxidative stress, as shown by increased MDA level and decreased activity of SOD, CAT, and GSH-Px. In addition, CYP2 caused a significant increase of 42% the concentration of total cholesterol and more than 75% in triglycerides compared to the control group. Furthermore, DNA fragmentation and collagen deposition were both amplified owing to CYP toxicity. This harmful effect was confirmed by a histological study using H-E and Sirius Red staining. Overall, our results clearly proved the cardiotoxicity caused by α-cypermethrin.

Cardioprotective effects of (E)-4-hydroxy-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide: a newly synthesized coumarin hydrazone against isoproterenol-induced myocardial infarction in a rat model.

The current study was carried out to evaluate the effect of pretreatment and co-treatment with a newly synthesized coumarin hydrazone, (E)-4-hydroxy-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide (hereinafter EK6), against isoproterenol-induced myocardial infarction in rats. Changes in biochemistry, cardiac biomarkers, electrocardiography, and histopathology after treatment with EK6 or acenocoumarol (Sintrom) were studied. Animals were randomly divided into 4 groups: vehicle control (C), isoproterenol + Sintrom (ISO + Sin), isoproterenol + EK6 (ISO + EK6), and isoproterenol (ISO). Myocardial infarction was induced by subcutaneous ISO administration at a dose of 85 mg·kg-1·day-1 with a drug-free interval of 24 h on days 6 and 7. Treatment with ISO led to significant elevation (p < 0.05) in serum levels of cardiac injury biomarkers, namely cardiac troponin-T, lactate dehydrogenase, creatine kinase-MB, alanine aminotransferase, and aspartate aminotransferase compared with levels in the vehicle control. A change in the lipid profile was also observed as a significant increase in total cholesterol and triglycerides. Furthermore, ISO caused significant alterations in the electrocardiogram pattern, including significant ST-segment elevation, significant decreased R wave amplitude, and significant increase in heart rate (16%) as well as marked changes in the histopathology of the heart tissue. Pretreatment and co-treatment with newly synthesized coumarin hydrazone restored all ISO-induced biochemical, lipid, cardiac, and histopathological changes in rats with myocardial infarction.

Contribution of adiponectin polymorphisms to the risk of coronary artery disease in a North-African Tunisian population.

BACKGROUND: Adiponectin, an adipocyte-derived protein, is known to play a key role in the processes leading to atherosclerosis and coronary artery disease (CAD) through its anti-atherogenic, anti-inflammatory, antioxidative, and anti-apoptotic properties. In the current study, we have studied the association of two single nucleotide polymorphisms (SNPs) +45 T>G (rs2241766) and +276 G>T (rs1501299) of the adiponectin gene with coronary artery disease (CAD) on an Arab/North-African population from Tunisia. METHODS: Subjects comprised 277 patients with angiographically demonstrated CAD and 269 age- and gender-matched control subjects. The adiponectin genotypes were performed by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The contribution of adiponectin variants to CAD was analyzed by haplotype and regression analysis. RESULTS: Adiponectin +45T>G and +276G>T genotypic and allelic distributions did not show a significant difference between cases and controls. Similarly, no association with CAD was observed for the haplotype analysis. Assuming dominant model of transmission for both polymorphisms and after adjustment of a number of traditional risk factors for CAD, logistic regression analysis showed an association of SNP +45 T>G with increased risk of developing CAD [adjusted OR (95% CI) = 2.59 (1.17-5.70); P = .01]. However, SNP + 276 G>T is associated with decreased risk of developing CAD [adjusted OR (95% CI) = 0.47 (0.22-0.97); P = .04]. CONCLUSION: There is no allelic or genotypic association of +45 T>G and +276 G>T of the adiponectin gene with CAD in the Tunisian population.