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Potential effect of new (E)‐4‐hydroxy ‐N’‐(1‐(7‐hydroxy‐2‐oxo‐2H‐chromen‐3‐yl) ethylidene) benzohydrazide against acute myocardial infarction: Haemodynamic,biochemical and histological studies
Authors:Kais Mnafgui,Emna Khdhiri,Raouf Hajji,Anouar Feriani,Francisco Ivan da Silva,Ant  nia Laí  res da Silva Santos,Abir Tlili,Souhail Mlayeh,Moncef Bouzidi,Houcine Ammar,Souhir Abid
Affiliation:Kais Mnafgui,Emna Khdhiri,Raouf Hajji,Anouar Feriani,Francisco Ivan da Silva,Antônia Laíres da Silva Santos,Abir Tlili,Souhail Mlayeh,Moncef Bouzidi,Houcine Ammar,Souhir Abid
Abstract:
This study aimed to explore the cardioprotective effect of new synthesized coumarin (E)‐4‐hydroxy‐N’‐(1‐(7‐hydroxy‐2‐oxo‐2H‐chromen‐3‐yl) ethylidene) benzohydrazide denoted (Hyd.Cou) against myocardial infarction disorders. Male Wistar rats were divided into four groups; Control, isoproterenol (ISO), ISO + Acenocoumarol (Ac) and ISO + Hyd.Cou. Results showed that the ISO group exhibited serious alteration in EGC pattern, significant heart hypertrophy (+33%), haemodynamic disturbance and increase in plasma rate of CK‐MB, LDH and troponin‐T by 44, 53, and 170%, respectively, as compared to Control. Moreover, isoproterenol induced a rise in plasma angiotensin‐converting enzyme activity (ACE) by 49%, dyslipidaemia, and increased thiobarbituric acid‐reactive substances (TBARS) by 117% associated with decrease in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 46% and 58%, respectively in myocardium. Interestingly, the molecular docking calculation demonstrated strong interactions of Hyd.Cou with the receptors of the protein disulphide isomerase (PDI) which could highlight the antithrombotic effect. Moreover, Hyd.Cou improved plasma cardiac dysfunction biomarkers, mitigated the ventricle remodelling process and alleviated heart oxidative stress damage. Overall, Hyd.Cou prevented the heart from the remodelling process through inhibition of ACE activity and oxidative stress improvement.
Keywords:coumarin  dyslipidaemia  molecular docking  myocardial infarction  oxidative stress  protein disulphide isomerase
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