Cytosolic NADPH-UQ reductase-linked recycling of cellular ubiquinol: its protective effect against carbon tetrachloride hepatotoxicity in rat.
To confirm whether or not cytosolic NADPH-UQ reductase is involved in the recycling of cellular ubiquinol (UQH2) consumed during lipid peroxidation, the effect of a UQ-10 supplement on the NADPH-UQ reductase and cellular defense against oxidative damage in rat livers was investigated. Supplements of UQ-10 for 14 days enhanced the levels of UQH2-10 and NADPH-UQ reductase in rat livers without any appreciable changes in other antioxidant contents and related enzyme activities. However, the injection of carbon tetrachloride (CCl4) into the rats induced lipid peroxidation and decreased the cellular UQH2-10 contents (and increased equivalent amounts of UQ-10), as well as decreasing the ascorbic acid, reduced glutathione (GSH) and alpha-tocopherol contents of the rat livers. Administration of the UQ-10 supplement prior to the CCl4 treatment spared alpha-tocopherol (but not GSH or ascorbic acid), inhibited lipid peroxidation, and thus improved CCl4-induced hepatitis. These findings support the notion that NADPH-UQ reductase in cytosol is the enzyme responsible for the regeneration of UQH2 from UQ formed by lipid peroxidation in cells.
Kishi
T
T
Faculty of Pharmaceutical Science, Kobe Gakuin University, Japan.
Takahashi
T
T
Okamoto
T
T
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control*; D003600:Cytosol / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
D014451:Ubiquinone; D002251:Carbon Tetrachloride; D016660:NAD(P)H Dehydrogenase (Quinone); C003741:ubiquinol; C030571:ubiquinone 9