Mechanisms of apoptosis in rat cerebellar granule cells induced by hydroxyl radicals and the effects of EGb761 and its constituents

In this study investigation is made on whether oxidative stress produced by treatment with hydroxyl radicals can induce apoptosis in rat cerebellar gr anule cells. The protective effects of Ginkgo biloba extract (EGb761) and i ts active constituents against apoptosis are also examined. The results sho w that hydroxyl radicals generated by the Fenton reaction induced apoptosis in cerebellar granule cells, which was associated with the decrease in the Bcl-2 mRNA level and the increase in the protein levels of the transcripti on factors Fos and Jun. Moreover. hydroxyl radicals induced time-dependent lipid peroxidation in cells and caused the changes in the sulfhydryl group binding sites on the membrane proteins. Hydroxyl radicals may induce apopto sis rin different signaling pathways. EGb761 attenuated these changes and i ts different constituents showed different effects. The total flavonoid com ponent of EGb761 and a mixture of flavonoids and terpenes protected cerebel lar granule cells from oxidative damage and apoptosis induced by hydroxyl r adicals. Total terpenes of EGb761 did not protect against apoptosis. Flavon oids and terpenes did not show a synergistic effect in this regard. (C) 200 0 Elsevier Science Ireland Ltd. All rights reserved.