Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: Role of nitric oxide, thioredoxin, and heme oxygenase

Mahesh Thirunavukkarasu, Suresh Varma Penumathsa, Srikanth Koneru, B. Juhász, Lijun Zhan, Hajime Otani, Debasis Bagchi, Dipak K. Das, Nilanjana Maulik

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Abstract

Excessive oxidative stress has been implicated in the pathology and complications of diabetes, which leads to myocardial ischemia reperfusion injury. The present study was designed to examine whether resveratrol (trans-3,5,4′-trihydroxystilbene), a polyphenolic compound present in red wine has a direct cardioprotective effect on diabetic myocardium. Resveratrol (2.5 mg/kg body wt/day) and L-NAME (25 mg/kg body wt/day) were administered orally for 15 days to streptozotocin (65 mg/kg)-induced diabetic rats. Sprague Dawley rats were divided into 5 groups: (i) control, (ii) diabetic, (iii) diabetic + resveratrol, (iv) diabetic + resveratrol + L-NAME (nitric oxide synthase inhibitor), and (v) diabetic + L-NAME. In our present study resveratrol demonstrated significant reduction in glucose level in diabetic rats. After the treatment, the hearts were excised and subjected to 30 min of global ischemia followed by 2 h of reperfusion. Resveratrol-treated diabetic rats demonstrated significant reduction in glucose levels as compared to the nontreated diabetic animals, and improved left ventricular function throughout reperfusion compared to the diabetic or L-NAME-treated animals (dp/dtmax 1457 ± 51 vs 999 ± 44 mm Hg/s at 120 min reperfusion). Cardioprotection from ischemic injury in resveratrol-treated diabetic rats showed decreased infarct size (42% vs 51%) and cardiomyocyte apoptosis (35% vs 40%) as compared with diabetic animals. Resveratrol produced significant induction of p-AKT, p-eNOS, Trx-1, HO-1, and VEGF in addition to increased activation of MnSOD activity in diabetic animals compared to nondiabetic animals. However treatment with L-NAME in resveratrol-treated and nontreated diabetic animals demonstrated significant downregulation of the above-noted protein expression profile and MnSOD activity. In the present study we found that the mechanism(s) responsible for the cardioprotective effect of resveratrol in the diabetic myocardium include upregulation of Trx-1, NO/HO-1, and VEGF in addition to increased MnSOD activity and reduced blood glucose level. Thus this study shows a novel mechanism of pharmacological preconditioning with resveratrol in the diabetic myocardium.

Original languageEnglish
Pages (from-to)720-729
Number of pages10
JournalFree Radical Biology and Medicine
Volume43
Issue number5
DOIs
Publication statusPublished - Sep 1 2007

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Heme Oxygenase (Decyclizing)
Thioredoxins
Experimental Diabetes Mellitus
Streptozocin
Medical problems
Nitric Oxide
NG-Nitroarginine Methyl Ester
Animals
Rats
Reperfusion
Myocardium
Vascular Endothelial Growth Factor A
resveratrol
Polyphenolic compounds
Myocardial Reperfusion Injury
Glucose
Oxidative stress
Wine
Pathology
Diabetes Complications

Keywords

  • Diabetes
  • Glucose
  • HO-1
  • Ischemia reperfusion
  • MnSOD
  • Thioredoxin

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes : Role of nitric oxide, thioredoxin, and heme oxygenase. / Thirunavukkarasu, Mahesh; Penumathsa, Suresh Varma; Koneru, Srikanth; Juhász, B.; Zhan, Lijun; Otani, Hajime; Bagchi, Debasis; Das, Dipak K.; Maulik, Nilanjana.

In: Free Radical Biology and Medicine, Vol. 43, No. 5, 01.09.2007, p. 720-729.

Research output: Contribution to journalArticle

Thirunavukkarasu, Mahesh ; Penumathsa, Suresh Varma ; Koneru, Srikanth ; Juhász, B. ; Zhan, Lijun ; Otani, Hajime ; Bagchi, Debasis ; Das, Dipak K. ; Maulik, Nilanjana. / Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes : Role of nitric oxide, thioredoxin, and heme oxygenase. In: Free Radical Biology and Medicine. 2007 ; Vol. 43, No. 5. pp. 720-729.
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