title: Edaravone, a potent free radical scavenger and a calcium channel blocker attenuate isoproterenol induced myocardial infarction by suppressing oxidative stress, apoptotic signaling and ultrastructural damage.
abstract: OBJECTIVE
  In the present study, we investigated whether combination therapy of low-dose benidipine with the potent free radical scavenger edaravone has a cardioprotective effect against isoproterenol (ISO)-induced myocardial infarction (MI) in Wistar rats.
  
  
  METHODS
  Rats were pretreated with concurrent doses of benidipine and edaravone (1 μg/kg/day + 1 mg/kg/day and 3 μg/kg/day + 3 mg/kg/day) by intravenous (i.v.) and intraperitoneal (i.p.) routes respectively for 28 days, followed by MI induction using ISO (85 mg/kg) by subcutaneous route for two days at 24 h intervals. After the treatment period, blood was withdrawn and the heart was preserved for biochemical estimations.
  
  
  RESULTS
  The activities of the cardiac biomarkers (lactate dehydrogenase and creatine kinase-MB), and the level of malondialdehyde (MDA) significantly increased, while antioxidant markers (reduced glutathione, catalase, superoxidase dismutase, glutathione peroxidase, glutathione reductase) were significantly decreased in the ISO intoxicated group compared with the control group. Moreover, the level of C-reactive protein (CRP) and Caspase-3 activity significantly increased in ISO-intoxicated group. An ultrastructure study was also carried out. Pretreatment with a combination of benidipine and edaravone significantly attenuated the activities of the cardiac biomarkers and the level of MDA, and significantly increased the antioxidant markers compared with the ISO-intoxicated group. Furthermore, pretreatment with the combination of benidipine and edaravone significantly decreased the level of CRP and Caspase-3 activity as compared to the ISO-treated group. The ultrastructure study of myocardium revealed that pretreated groups preserved the mitochondrial shape, the membrane and its internal structures.
  
  
  CONCLUSIONS
  Taken together these results suggest that the combination of benidipine and edaravone showed significant protective effect in ISO-induced MI.
authors: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors: Md Quamrul
authors: MQ
authors: Hassan
authors: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors: Md Sayeed
authors: MS
authors: Akhtar
authors: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors: Mohd
authors: M
authors: Akhtar
authors: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors: Javed
authors: J
authors: Ali
authors: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors: Syed Ehtaishamul
authors: SE
authors: Haque
authors: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India aknajmi@jamiahamdard.ac.in.
authors: Abul Kalam
authors: AK
authors: Najmi
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002097:C-Reactive Protein / Q000032:analysis; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D000077553:Edaravone; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009203:Myocardial Infarction / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000648:ultrastructure*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D016166:Free Radical Scavengers; C061004:benidipine; D008315:Malondialdehyde; D002097:C-Reactive Protein; D053148:Caspase 3; D007545:Isoproterenol; D000077553:Edaravone; D000983:Antipyrine
keywords: benidipine; isoproterenol; myocardial infarction; oxidative stress; ultrastructure damage