Alprostadil attenuates myocardial ischemia/reperfusion injury by promoting antioxidant activity and eNOS activation in rats

Acta Cir Bras. 2018 Dec;33(12):1067-1077. doi: 10.1590/s0102-865020180120000004.

Abstract

Purpose: To investigate the effect of alprostadil on myocardial ischemia/reperfusion (I/R) in rats.

Methods: Rats were subjected to myocardial ischemia for 30 min followed by 24h reperfusion. Alprostadil (4 or 8 μg/kg) was intravenously administered at the time of reperfusion and myocardial infarct size, levels of troponin T, and the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were measured. Antioxidative parameters, nitric oxide (NO) content and phosphorylated endothelial nitric oxide synthase 3 (p-eNOS) expression in the left ventricles were also measured. Histopathological examinations of the left ventricles were also performed.

Results: Alprostadil treatment significantly reduced myocardial infarct size, serum troponin T levels, and CK-MB and LDH activity (P<0.05). Furthermore, treatment with alprostadil significantly decreased malondialdehyde (MDA) content (P<0.05) and markedly reduced myonecrosis, edema and infiltration of inflammatory cells. Superoxide dismutase and catalase activities (P<0.05), NO level (P<0.01) and p-eNOS (P<0.05) were significantly increased in rats treated with alprostadil compared with control rats.

Conclusion: These results indicate that alprostadil protects against myocardial I/R injury and that these protective effects are achieved, at least in part, via the promotion of antioxidant activity and activation of eNOS.

Publication types

  • Evaluation Study

MeSH terms

  • Alprostadil / pharmacology*
  • Animals
  • Antioxidants / pharmacology*
  • Blotting, Western
  • Catalase / analysis
  • Creatine Kinase, MB Form / blood
  • Creatine Kinase, MB Form / drug effects
  • Enzyme Activation / drug effects
  • Heart Ventricles / drug effects
  • Heart Ventricles / pathology
  • L-Lactate Dehydrogenase / blood
  • L-Lactate Dehydrogenase / drug effects
  • Male
  • Malondialdehyde / analysis
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Nitric Oxide / analysis
  • Nitric Oxide Synthase Type III / metabolism*
  • Oxidative Stress / drug effects
  • Random Allocation
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Superoxide Dismutase / analysis
  • Treatment Outcome
  • Troponin T / blood
  • Troponin T / drug effects

Substances

  • Antioxidants
  • Troponin T
  • Nitric Oxide
  • Malondialdehyde
  • L-Lactate Dehydrogenase
  • Catalase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Superoxide Dismutase
  • Creatine Kinase, MB Form
  • Alprostadil