(E)-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide protecting rat heart tissues from isoproterenol toxicity: Evidence from in vitro and in vivo tests.

ABSTRACT

The current study was aimed to assess the protective effect of a new molecule (E)-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide, denoted 1c, against cardiac remodeling process in isoproterenol (Isop) induced myocardial infarction (MI) in rats. Male Wistar rats were randomly divided into four groups, control, Isop (85 mg/kg body weight was injected subcutaneously into rats at an interval of 24 h for 2 days (6th and 7th day) to induce MI and pretreated animals with acenocoumarol (Ace) (150 µg/kg bw) and 1c (150 µg/kg bw) by oral administration during 7 days and injected with isoproterenol (Isop + Ace) and (Isop + 1c) groups. Results in vitro showed that 1c is endowed with potent inhibition of angiotensin-converting enzyme (ACE) with an IC50 39.12 µg/ml. The in vivo exploration evidenced alteration in the ECG pattern, notable cardiac hypertrophy and increase in plasma level of fibrinogen, troponin-T, CK-MB and LDH, AST and ALT by 171%, 300%, 50%, 64% and 75% respectively with histological myocardium necrosis and cells inflammatory infiltration. However, pre-treatment with 1c improved the ECG pattern reduced significantly the cardiac dysfunction markers and ameliorated the thrombolytic process by decreasing fibrinogen level as compared to untreated infracted rats. Overall, (E)-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide 1c could be used as anticoagulant agent to prevent thrombosis in acute myocardial infarction.