Inhibition of nadph-dependent microsomal protein oxidation by Ginkgo biloba extract (EGb 761): Implication on its potential protective effect against ethanol-induced fatty liver

Accumulation of lipids in the liver is the most common disturbance of lipid metabolism produced by ethanol. Increased production of reactive oxygen species (ROS) is considered to be one of the mechanisms by which ethanol induces hepatotoxicity. In view of interest in the use of natural compound as a hepatoprotector, we evaluated the in vitro antioxidant ability of Ginkgo biloba extract (EGb 761) for its inhibition of protein oxidation in the NADPH-dependent hepatic microsomal oxidizing system. Apolipoprotein E (apoE) was used as a specific target protein of ROS because it plays an important role in the hepatic lipid metabolism and very low density lipoprotein secretion. Addition of NADPH initiated microsomal ROS production, leading to selective modification of microsomal proteins. Recombinant apoE was also modifided as estimated by sodium dodecyl sulfate-polyacrylamide gel-electrophoresis. EGb 761 at the concentration as low as 6 μg/ml effectively inhibited NADPH-dependent production of ROS in the microsomal fraction and prevented oxidation of apoE and microsomal proteins. Glutathione and ascorbic acid also prevented the processes in a dose-dependent manner. These results suggest that EGb 761 may serve as an antioxidant active in reducing the extent of oxidative liver injury and that it could be potentially useful for preventing ethanol-induced fatty liver.