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

• Published in: Canadian journal of physiology and pharmacology 2019-10, Vol.97 (10), p.989-998
• Main Authors: Ghazouani, Lakhdar, Khdhiri, Emna, Elmufti, Afoua, Feriani, Anouar, Tir, Meriam, Baaziz, Intissar, Hajji, Raouf, Ben Mansour, Hedi, Ammar, Houcine, Abid, Souhir, Mnafgui, Kais
• Format: Article
• Language: English
• Subjects: Alanine; Alanine transaminase; Animals; Aspartate aminotransferase; Benzopyrans - administration & dosage; Benzopyrans - chemical synthesis; Biochemistry; Biomarkers; Biomarkers - analysis; Calcium-binding protein; cardioprotection; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - chemical synthesis; Cholesterol; Coumarin; coumarin derivative; Coumarins - administration & dosage; Coumarins - chemical synthesis; Creatine; Creatine kinase; Disease Models, Animal; dérivé de la coumarine; ECG; EKG; Electrocardiography; Heart - drug effects; Heart attacks; Heart rate; Heart Rate - drug effects; Histopathology; Humans; Hydrazones; Hydrazones - administration & dosage; Hydrazones - chemical synthesis; infarctus du myocarde; Isoproterenol; Isoproterenol - toxicity; isoprotérénol; L-Lactate dehydrogenase; Lactic acid; Lipids; Male; Medical research; Myocardial infarction; Myocardial Infarction - chemically induced; Myocardial Infarction - diagnosis; Myocardial Infarction - drug therapy; Myocardium - pathology; Pharmacology; Physiology; Rats; Rats, Wistar; Rodents; Serum levels; Studies; Treatment Outcome; Triglycerides; Troponin
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2019-0085

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.