Protection of mitochondrial respiration activity by bilobalide

Mitochondria alteration is an early event in ischemia-induced damage, and i ts prevention improves tissue survival upon reperfusion. Adenine translocas e and complex I activities are rapidly affected by ischemia. Ginkgo biloba extract demonstrates anti-ischemic properties attributable to the terpenoid fraction, mainly due to the presence of bilobalide. The mechanism of the p rotection afforded by bilobalide is not yet known. In this work, the effect s of bilobalide on mitochondrial respiration were investigated. Mitochondri a isolated from rats treated with bilobalide (2 to 8 mg/kg) showed a dose-d ependent increase in the respiratory control ratio, due to a lower oxygen c onsumption during state 4. Bilobalide also decreased the sensitivity of oxy gen consumption to inhibition of complex I by Amytal or to inhibition of co mplex III by antimycin A or myxothiazol. There was no protection of complex es IV and V. It also increased the activity of complex I but not of adenine translocase. Similar effects were also obtained in vitro when control mito chondria were preincubated for 1 hr with 0.8 mu g/mL bilobalide. Treatment of the rats with 8 mg/kg bilobalide also prevented the ischemia-induced dec rease in state 3 of the mitochondrial respiration and thus the decrease in RCR. The protective effect of bilobalide on cellular ATP content observed u nder ischemic conditions can be correlated with the above observations. By protecting complex I and III activities, bilobalide allows mitochondria to maintain their respiratory activity under ischemic conditions as long as so me oxygen is present, thus delaying the onset of ischemia-induced damage. T his mechanism provides a possible explanation for the anti ischemic propert ies of bilobalide and of Ginkgo biloba extract in therapeutic interventions . BIOCHEM PHARMACOL 58;1: 109-119, 1999. (C) 1999 Elsevier Science Inc.