The effect of Ginkgo biloba in isolated ischemic/reperfused rat heart: a link between vitamin E preservation and prostaglandin biosynthesis.
The effect of Ginkgo biloba extract (EGb 761) was studied in rat hearts submitted to ischemia/reperfusion. Isolated hearts perfused in Langendorff mode were subjected to 60 minutes of global ischemia and 15 minutes of reperfusion. EGb 761 was administered by chronic or acute treatment: intra-peritoneal injections of 5 mg/Kg extract for 5 days, or 100 mg /L extract addition to the perfusion buffer, respectively. In hearts not treated with EGb 761, ischemia induced a 20% decrease in the concentration of membrane alpha-tocopherol. This effect was not worsened by reperfusion. alpha-tocopherol consumption was accompanied by about 650% increase in 6-ketoPGF1alpha release within 3 minutes of reperfusion. Moreover, ischemia induced activation of transcription factor NF-kappaB, as compared with the untreated group. In both chronic and acute treatment with EGb 761, heart concentration of alpha-tocopherol was completely spared during ischemia as much as after reperfusion, and a significant decrease of 6-ketoPGF1alpha release was observed at 3 minutes of reperfusion. Nuclear translocation of NF-kappaB was lowered during ischemia. EGb 761 might act as direct free radical scavenger or as tocopheryl radical recycler; in both cases sparing membrane vitamin E should affect phospholipase A2 activity. Finally, EGb 761, by lowering ROS produced during ischemia, challenges nuclear translocation of NF-kappaB.
Kusmic
Claudia
C
Institute of Clinical Physiology, CNR, Pisa, Italy. kusmic@ifc.cnr.it
Basta
Giuseppina
G
Lazzerini
Guido
G
Vesentini
Nicoletta
N
Barsacchi
Renata
R
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005260:Female; D005612:Freeze Drying; D020441:Ginkgo biloba; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D014810:Vitamin E / Q000737:chemistry / Q000378:metabolism*; D000096983:Ginkgo Extract
D015121:6-Ketoprostaglandin F1 alpha; D007770:L-Lactate Dehydrogenase; D016328:NF-kappa B; D010936:Plant Extracts; D014157:Transcription Factors; D014810:Vitamin E; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract