Sustained protective effects of 7-monohydroxyethylrutoside in an in vivo model of cardiac ischemia-reperfusion.
Earlier studies have shown that 7-monohydroxyethylrutoside (monoHER), an antioxidant flavonoid, protects against doxorubicin-induced cardiotoxicity. In this study, we investigated potential sustained cardioprotective effects of monoHER in a model of ischemia-reperfusion (I/R) in mice. Ischemia was induced for 30 min by ligating the left anterior descending coronary artery. Afterwards, the ligature was removed and reperfusion was allowed for 6 or 24 h or 2 weeks. MonoHER (500 mg/kg) was given intraperitoneally (i.p.) one hour before ischemia. Treatment with monoHER significantly attenuated myocardial neutrophil influx both at 6 and 24 h after reperfusion by 77% and 76%, respectively. Infarct size was also significantly reduced, 24 h and 2 weeks after reperfusion by 58% and 49%, respectively. Whereas ischemia-reperfusion had no influence on basal levels of cardiac contractility (+dp/dt), responses to dobutamine were blunted 24 h and 2 weeks after reperfusion. In mice treated with monoHER, cardiac contractility response was significantly restored. These results indicate that monoHER exerts a sustained cardioprotective effect on ischemia-reperfusion injury and prevents deterioration of cardiac contractility.
De Celle
Tijl
T
Department of Pharmacology, Cardiovascular Research Institute Maastricht, Universiteit Maastricht, P.O. Box, 6200 MD, Maastricht, The Netherlands. t.decelle@farmaco.unimaas.nl
Heeringa
Peter
P
Strzelecka
Agnieska E
AE
Bast
Aalt
A
Smits
Jos F
JF
Janssen
Ben J
BJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006896:Hydroxyethylrutoside / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D016276:Ventricular Function / Q000187:drug effects
D002316:Cardiotonic Agents; D006896:Hydroxyethylrutoside; D004280:Dobutamine