(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

Eur J Pharmacol. 2020 Aug 15:881:173137. doi: 10.1016/j.ejphar.2020.173137. Epub 2020 May 4.

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.

Keywords: (E)-N’-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide; ACE; Isoproterenol; Myocardial infarction; Thrombolytic.

MeSH terms

  • Action Potentials / drug effects
  • Angiotensin-Converting Enzyme Inhibitors / chemical synthesis
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / pharmacology
  • Biomarkers / blood
  • Cardiotoxicity
  • Disease Models, Animal
  • Fibrinogen / metabolism
  • Fibrinolytic Agents / chemical synthesis
  • Fibrinolytic Agents / pharmacology*
  • Heart Rate / drug effects
  • Hydrazones / chemical synthesis
  • Hydrazones / pharmacology*
  • Isoproterenol
  • Lipids / blood
  • Male
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Necrosis
  • Rats, Wistar
  • Ventricular Remodeling / drug effects

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Inflammatory Agents
  • Biomarkers
  • Fibrinolytic Agents
  • Hydrazones
  • Lipids
  • Fibrinogen
  • Isoproterenol