HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Evidence that hydroxysafflor yellow A protects the heart against ischaemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening.

Abstract
1. The present study was conducted to investigate whether hydroxysafflor yellow A (HSYA) has a protective effect against heart injury after ischaemia-reperfusion and to determine the possible mechanism involved. 2. Hearts isolated from male Sprague-Dawley rats were perfused on a Langendorff apparatus and subjected to 30 min global ischaemia, followed by 120 min reperfusion. Infarct size and the level of lactate dehydrogenase (LDH) in the coronary effluent were determined. In mitochondria from isolated perfused hearts, Ca(2+)-induced swelling was observed. In isolated ventricular myocytes, depolarization of the mitochondrial membrane was determined by tetramethyl-rhodamine ethyl ester (TMRE) fluorescence. Furthermore, levels of phosphorylated endothelial nitric oxide synthase (eNOS) protein were measured by western blot. 3. Pretreatment with HSYA for 5 min before ischaemia reduced infarct size and the release of LDH. Administration of 20 micromol/L atractyloside, an opener of the mitochondrial permeability transition pore, and 10 micromol/L N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, attenuated the protective effects of HSYA. In mitochondria isolated from hearts pretreated with 0.1 mmol/L HSYA for 5 min, a significant inhibition of Ca(2+)-induced swelling was observed and this inhibition was attenuated by l-NAME. In isolated ventricular myocytes, pretreatment with HSYA prevented ischaemia-induced cell death and depolarization of the mitochondrial membrane, whereas atractyloside or l-NAME attenuated the effects of HSYA. Levels of phosphorylated eNOS protein were significantly enhanced in the HSYA-treated group. 4. The findings of the present study indicate that HSYA protects the myocardium against ischaemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening. The effect of HSYA on mitochondrial permeability transition pore opening may be mediated through enhanced nitric oxide production by eNOS activation.
AuthorsYi-Na Liu, Zhong-Min Zhou, Peng Chen
JournalClinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 35 Issue 2 Pg. 211-6 (Feb 2008) ISSN: 1440-1681 [Electronic] Australia
PMID17941891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cardiovascular Agents
  • Enzyme Inhibitors
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Quinones
  • hydroxysafflor yellow A
  • Atractyloside
  • Nitric Oxide
  • Chalcone
  • L-Lactate Dehydrogenase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • NG-Nitroarginine Methyl Ester
Topics
  • Animals
  • Atractyloside (pharmacology)
  • Cardiovascular Agents (pharmacology, therapeutic use)
  • Cell Survival (drug effects)
  • Chalcone (analogs & derivatives, pharmacology, therapeutic use)
  • Enzyme Inhibitors (pharmacology)
  • In Vitro Techniques
  • L-Lactate Dehydrogenase (metabolism)
  • Male
  • Membrane Potential, Mitochondrial (drug effects)
  • Mitochondria, Heart (drug effects, metabolism, pathology)
  • Mitochondrial Membrane Transport Proteins (antagonists & inhibitors, metabolism)
  • Mitochondrial Permeability Transition Pore
  • Mitochondrial Swelling
  • Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
  • Myocytes, Cardiac (drug effects, metabolism, pathology)
  • NG-Nitroarginine Methyl Ester (pharmacology)
  • Nitric Oxide (metabolism)
  • Nitric Oxide Synthase Type II (antagonists & inhibitors, metabolism)
  • Nitric Oxide Synthase Type III
  • Perfusion
  • Phosphorylation
  • Quinones (pharmacology, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: