title: Hemin, a heme oxygenase-1 inducer, restores the attenuated cardioprotective effect of ischemic preconditioning in isolated diabetic rat heart.
abstract: BACKGROUND
  Attenuated cardioprotective effect of ischemic preconditioning (IPC) by reduced nitric oxide (NO) is a hallmark during diabetes mellitus (DM). Recently, we reported that the formation of caveolin-endothelial nitric oxide synthase (eNOS) complex decreases the release of NO, which is responsible for attenuation of IPC-induced cardioprotection in DM rat heart. Heme oxygenase-1 (HO-1) facilitates release of NO by disrupting caveolin-eNOS complex. The activity of HO-1 is decreased during DM. This study was designed to investigate the role of hemin (HO-1 inducer) in attenuated cardioprotective effect of IPC in isolated diabetic rat heart.
  
  
  METHODS
  DM was induced in male Wistar rat by single dose of streptozotocin. Cardioprotective effect was assessed in terms of myocardial infarct size and release of lactate dehydrogenase and creatine kinase in coronary effluent. The release of NO was estimated indirectly by measuring the release of nitrite in coronary effluent. Perfusion of sodium nitrite, a precursor of NO, was used as a positive control.
  
  
  RESULTS
  IPC-induced cardioprotection and increased release of nitrite were significantly attenuated in a diabetic rat as compared to a normal rat. Pretreatment with hemin and daidzein, a caveolin inhibitor, alone or in combination significantly restored the attenuated cardioprotection and increased the release of nitrite in diabetic rat heart. Zinc protoporphyrin, a HO-1 inhibitor, significantly abolished the observed cardioprotection and decreased the release of nitrite in hemin pretreated DM rat heart.
  
  
  CONCLUSIONS
  Thus, it is suggested that hemin restores the attenuated cardioprotective effect in diabetic rat heart by increasing the activity of HO-1 and subsequently release of NO.
authors.affiliation: 1 Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India.
authors.forename: I
authors.initials: I
authors.lastname: Gupta
authors.affiliation: 2 Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.
authors.forename: A
authors.initials: A
authors.lastname: Goyal
authors.affiliation: 2 Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.
authors.forename: N K
authors.initials: NK
authors.lastname: Singh
authors.affiliation: 3 All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: H N
authors.initials: HN
authors.lastname: Yadav
authors.affiliation: 1 Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India.
authors.forename: P L
authors.initials: PL
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D004790:Enzyme Induction / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology*; D019194:Ischemic Preconditioning; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D006427:Hemin; D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1; D003402:Creatine Kinase
keywords: Heme oxygenase-1; daidzein; diabetic rat heart; hemin; ischemic preconditioning