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.
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-hepatitis, and it decreased the liver levels of L-ascorbic acid, reduced form of glutathione (GSH), alpha-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, alpha-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.
Takahashi
T
T
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Sugimoto
N
N
Takahata
K
K
Okamoto
T
T
Kishi
T
T
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000975:Antioxidants; D014451:Ubiquinone; D002251:Carbon Tetrachloride; D016660:NAD(P)H Dehydrogenase (Quinone); D005978:Glutathione; C003741:ubiquinol