Cellular Antioxidant Defense by a Ubiquinol-Regenerating System Coupled with Cytosolic NADPH-Dependent Ubiquinone Reductase : Protective Effect against Carbon Tetrachloride-Induced Hepatotoxicity in the Rat

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We found that NADPH-dependent ubiquinone reductase (NADPH-UQ reductase) in rat liver cytosol reduces ubiquinone (UQ) to ubiquinol (UQH₂) in lipid membranes and consequently inhibits lipid peroxidation [Takahashi T., et al., Biochem. J., 309, 883-890 (1995)]. Here we examined whether or not this UQH₂-regenerating system functions as a cellular antioxidant defense in animals. Rats were given UQ-10 for 2 weeks, and were then exposed to carbon tetrachloride (CCl₄). The UQ-10 supplement increased only in the NADPH-UQ reductase and the UQH₂-10 pool of rat liver without any appreciable change in the levels of other antioxidant factors. On the other hand, CCl₄ markedly increased plasma aspartate aminotransferase and alanine aminotransferase, liver weight and thiobarbituric acid reacting substances formation, which are indicators of CCl₄-hepat itis, and it decreased the liver levels of L-ascorbic acid, reduced form of glutathione (GSH), α-tocopherol, NADPH-UQ reductase and glutathione S-transferase. However, all the above indicators of CCl₄-induced hepatitis were significantly improved in rats given UQ-10. Furthermore, α-tocopherol, but neither L-ascorbic acid nor GSH, was significantly saved. UQ-10 supplement also was recovered glutathione S-transferase and NADPH-UQ reductase activities slightly. These results indicated that UQ-10 given to rats increased the cellular UQH₂-10 pool and cytosolic NADPH-UQ reductase activity in their livers, resulting in the inhibition of lipid peroxidation in the biomembranes, and consequently protected the rats from the CCl₄-hepatotoxicity.