PROTECTION OF HYPOXIA-INDUCED ATP DECREASE IN ENDOTHELIAL-CELLS BY GINKGO-BILOBA EXTRACT AND BILOBALIDE

Due to their localization at the interface between blood and tissue, e ndothelial cells are the first target of any change occurring within t he blood, and alterations of their functions can seriously impair orga ns. During hypoxia, which mimics in vivo ischemia, a cascade of events occurs in the endothelial cells, starting with a decrease in ATP cont ent and leading to their activation and release of inflammatory mediat ors. EGb 761 and one of its constituents, bilobalide, were shown to in hibit the hypoxia-induced decrease in ATP content in endothelial cells in vitro. Under these conditions, glycolysis was activated, as eviden ced by increased glucose transport, as well as increased lactate produ ction. Bilobalide was found to increase glucose transport under normox ic but not hypoxic conditions. In addition, EGb and bilobalide prevent ed the increase in total lactate production observed after 60 min of h ypoxia. However, after 120 min of hypoxia, the total lactate productio n was similar under normoxic and hypoxic conditions, and both compound s increased this production. These results indicate that glycolysis sl owed down between the 60th and 120th minute of hypoxia, while EGb and bilobalide delayed the onset of glycolysis activation. In another expe rimental model, both compounds were shown to increase the respiratory control ratio of mitochondria isolated from liver of rats treated oral ly. Since ischemia is known to uncouple mitochondria, the protection o f ATP content and the delay in glycolysis activation observed during h ypoxia in the presence of EGb 761 or bilobalide is best explained by a protection of mitochondrial respiratory activity, at least during the first 60 min of hypoxia incubation. Both products retain the ability to form ATP, thereby reducing the cell's need to induce glycolysis, pr obably by preserving ATP regeneration by mitochondria as long as oxyge n is available.