Protection by bilobalide of the ischaemia-induced alterations of the mitochondrial respiratory activity.
Ischaemia is a common feature of most vascular diseases. There is evidence from experimental and clinical studies that Ginkgo biloba extract protects tissues from ischaemia/reperfusion damages. Bilobalide seems to be responsible, at least in part, for this activity. However, the mechanism of the protection afforded by bilobalide is not yet known. In this work, the effects of bilobalide on mitochondrial respiration were investigated during liver and brain ischaemia, since mitochondria alteration is an early event in ischaemia-induced damage. Bilobalide could prevent the decrease in respiratory activity induced by ischaemia in liver and in brain, both when glutamate/malate or succinate was used as substrate. Ischaemia decreased state 3 respiration rate and bilobalide prevented this decrease. While bilobalide was not able to prevent the decrease in adenine translocase activity, it protected complex I activity. Bilobalide allows mitochondria to maintain their respiratory activity in ischaemic conditions by protecting complex I and probably complex III activities. Hence, the energetic pool of tissues is preserved during the ischaemic period as well as its viability. This mechanism provides, a possible explanation for the anti-ischaemic properties of bilobalide and of Ginkgo biloba extract in therapeutic interventions.
Janssens
D
D
Laboratoire de biochimie et biologie cellulaire, Facultés universitaires Notre-Dame de la Paix, 61, rue de Bruxelles, 5000 Namur, Belgium.
Delaive
E
E
Remacle
J
J
Michiels
C
C
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control; D003517:Cyclopentanes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005663:Furans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D046934:Ginkgolides; D007511:Ischemia / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D008099:Liver / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D003517:Cyclopentanes; D004224:Diterpenes; D005663:Furans; D046934:Ginkgolides; D000226:Mitochondrial ADP, ATP Translocases; D009245:NADH Dehydrogenase; C073710:bilobalide