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(E)-N'-(1-(7-Hydroxy-2-Oxo-2H-Chromen-3-Yl) Ethylidene) Benzohydrazide, a Novel Synthesized Coumarin, Ameliorates Isoproterenol-Induced Myocardial Infarction in Rats through Attenuating Oxidative Stress, Inflammation, and Apoptosis.

Abstract
The present study was directed to investigate the effect of precotreatment with (E)-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide (7-hyd.HC), a novel potent synthesized coumarin, on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. The hydrazone compound was characterized by IR, 1D, and 2D NMR analyses. Experimental induction of MI in rats was established by ISO (85 mg/kg/day, s.c) for two consecutive days (6th and 7th days). 7-hyd.HC or sintrom was given for 7 days prior and simultaneous to ISO injection. 7-hyd.HC offered a cardiopreventive effect by preventing heart injury marker leakage (LDH, ALT, AST, CK-MB, and cTn-I) from cardiomyocytes and normalizing cardiac function and ECG pattern, as well as improving lipid profile (TC, TG, LDL-C, and HDL-C), which were altered by ISO administration. Moreover, 7-hyd.HC precotreatment significantly mitigated the oxidative stress biomarkers, as evidenced by the decrease of lipid peroxidation and the increased level of the myocardial GSH level together with the SOD, GSH-Px, and catalase activities. 7-hyd.HC inhibited the cardiac apoptosis by upregulating the expression of Bcl-2 and downregulating the expression of Bax and caspase-3 genes. In addition, 7-hyd.HC reduced the elevated fibrinogen rate and better prevented the myocardial necrosis and improved the interstitial edema and neutrophil infiltration than sintrom. Overall, 7-hyd.HC ameliorated the severity of ISO-induced myocardial infarction through improving the oxidative status, attenuating apoptosis, and reducing fibrinogen production. The 7-hyd.HC actions could be mediated by its antioxidant, antiapoptotic, and anti-inflammatory capacities.
AuthorsAnouar Feriani, Emna Khdhiri, Meriam Tir, Afoua Elmufti, Nizar Tlili, Raouf Hajji, Houcine Ammar, Noureddine Allouche, Souhir Abid, Lakhdar Ghazouani, Kais Mnafgui
JournalOxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2020 Pg. 2432918 ( 2020) ISSN: 1942-0994 [Electronic] United States
PMID32215169 (Publication Type: Journal Article)
CopyrightCopyright © 2020 Anouar Feriani et al.
Chemical References
  • (E)-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide
  • Anti-Inflammatory Agents
  • Benzopyrans
  • Biomarkers
  • Coumarins
  • Hydrazones
  • Isoproterenol
Topics
  • Animals
  • Anti-Inflammatory Agents (chemical synthesis, chemistry, therapeutic use)
  • Apoptosis (drug effects)
  • Benzopyrans (chemical synthesis, chemistry, therapeutic use)
  • Biomarkers (metabolism)
  • Coumarins (chemical synthesis, chemistry, therapeutic use)
  • Hydrazones (chemical synthesis, chemistry, therapeutic use)
  • Inflammation (metabolism)
  • Isoproterenol (toxicity)
  • Male
  • Molecular Structure
  • Myocardial Infarction (chemically induced, drug therapy, metabolism, pathology)
  • Myocardium (metabolism)
  • Oxidative Stress (drug effects)
  • Rats
  • Rats, Wistar
  • Treatment Outcome

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