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Tetramethylpyrazine induces heme oxygenase-1 expression and attenuates myocardial ischemia/reperfusion injury in rats

Journal of Biomedical Science volume 13, pages 731–740 (2006)Cite this article

Abstract

The accumulation of oxygen free radicals and activation of neutrophils are strongly implicated as pathophysiological mechanisms mediating myocardial ischemia/reperfusion injury. Heme oxygenase-1 (HO-1) has been reported to play a protective role in oxidative tissue injuries. In this study, the cardioprotective activity of tetramethylpyrazine (TMP), an active ingredient of Chinese medicinal herb Ligusticum wallichii Franchat, was evaluated in an open-chest anesthetized rat model of myocardial ischemia/reperfusion injury. Pretreatment with TMP (5 and 10 mg/kg, i.v.) before left coronary artery occlusion significantly suppressed the occurrence of ventricular fibrillation. After 45 min of ischemia and 1 h of reperfusion, TMP (5 and 10 mg/kg) caused a significant reduction in infarct size and induced HO-1 expression in ischemic myocardium. The HO inhibitor ZnPP (50 µg/rat) markedly reversed the anti-infarct action of TMP. Superoxide anion production in ischemic myocardium after 10 min reperfusion was inhibited by TMP. Furthermore, TMP (200 and 500 µM) significantly suppressed fMLP (800 nM)-activated human neutrophil migration and respiratory burst. In conclusion, TMP suppresses ischemia-induced ventricular arrhythmias and reduces the infarct size resulting from ischemia/reperfusion injury in vivo. This cardioprotective activity of TMP may be associated with its antioxidant activity via induction of HO-1 and with its capacity for neutrophil inhibition.

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Acknowledgements

This study was supported by research grant from the Nation Science Council (NSC93–2320-B-016–039 to YM Lee), Taipei, Taiwan, ROC.

Author information

Affiliations

  1. Department of Nursing, HungKuang University, Taichung, Taiwan

    Shu-Ying Chen

  2. Department of Pharmacology, Taipei Medical University, Taipei, Taiwan

    George Hsiao

  3. Division of Cardiology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

    Hwong-Ru Hwang

  4. Department of Pharmacology, National Defense Medical Center, No.161, Section 6, Min-Chuan East Road, NeiHu 114, Taipei, Taiwan

    Pao-Yun Cheng & Yen-Mei Lee

Authors
  1. Shu-Ying Chen
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  2. George Hsiao
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  3. Hwong-Ru Hwang
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  4. Pao-Yun Cheng
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  5. Yen-Mei Lee
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Correspondence to Yen-Mei Lee.

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Chen, SY., Hsiao, G., Hwang, HR. et al. Tetramethylpyrazine induces heme oxygenase-1 expression and attenuates myocardial ischemia/reperfusion injury in rats. J Biomed Sci 13, 731–740 (2006). https://doi.org/10.1007/s11373-006-9098-2

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  • DOI: https://doi.org/10.1007/s11373-006-9098-2

Keywords

  • arrhythmias
  • HO-1
  • myocardial ischemia
  • neutrophils
  • oxidative stress
  • reperfusion injury
  • tetramethylpyrazine