tocopherylquinone and alpha-tocopherol-quinol

Recent reports indicate that both orally administered and topically applied alpha-tocopherol (vitamin E, TH) prevent UVB-induced skin carcinogenesis in mice. Because UVB exposure causes the formation of oxidants associated with tumor promotion, epidermal TH status may be an important determinant of susceptibility to photocarcinogenesis. To test this hypothesis, we studied the status of epidermal TH in C3H mice following exposure to single and repeated UVB exposures at doses typical of chronic photocarcinogenesis protocols. Exposure of mice to a single 13 kJ/m(2) dose over 60 min resulted in no acute depletion of epidermal TH and a modest increase in TH within 6-12 h. Daily exposure to 6.5 kJ/m(2) over 30 min resulted in a gradual increase in epidermal TH, which reached 5-fold after five daily exposures. The increase in epidermal TH was accompanied by an increase in the TH oxidation products alpha-tocopherolquinone (TQ) and alpha-tocopherolhydroquinone (THQ). We also studied the effect of the prooxidant chemical tumor promoter benzoyl peroxide and the prooxidant azo initiators azobis(amidinopropane HCl) and azobis(2, 4-dimethylvaleronitrile). Topical application of these prooxidant chemicals acutely oxidized epidermal TH to TQ and THQ. Topical treatments with the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) increased epidermal TH levels without producing a significant accumulation of TH oxidation products. The results indicate that UVB and tumor promoting chemicals all exert qualitatively different effects on epidermal TH status and that UVB and TPA trigger an adaptive response involving epidermal TH accumulation.

Topics: alpha-Tocopherol; Amidines; Animals; Antioxidants; Azo Compounds; Benzoyl Peroxide; Carcinogens; Cocarcinogenesis; Epidermis; Female; Hydroquinones; Mice; Mice, Inbred C3H; Nitriles; Oxidative Stress; Photochemistry; Tetradecanoylphorbol Acetate; Ultraviolet Rays; Vitamin E

Alpha-tocopherolhydroquinone (TQH2) is a product of alpha-tocopherol oxidation/reduction that exerts antioxidant effects in biological systems. TQH2 inhibited autoxidation of methyl linoleate initiated by peroxyl radicals derived from thermolysis of 2,2'-azobis(2,4-dimethylvaleronitrile) in acetonitrile. TQH2 oxidation yielded alpha-tocopherolquinone (TQ) as a major product and 2,3-epoxy-alpha-tocopherolquinone and 5,6-epoxy-alpha-tocopherolquinone as minor products. Each TQH2 consumed approximately two peroxyl radicals in the course of the oxidation. The data suggest that TQH2 scavenges peroxyl radicals primarily by electron transfer to form TQ and secondarily by addition-elimination to form the epoxyquinones.

Topics: alpha-Tocopherol; Antioxidants; Epoxy Compounds; Free Radical Scavengers; Hydroquinones; Kinetics; Linoleic Acids; Molecular Structure; Oxidation-Reduction; Peroxides; Vitamin E

The contents of alpha-tocopherolhydroquinone (TQH2), alpha-tocopherolquinone (TQ) and alpha-tocopherol (Toc) in isolated rat hepatocytes and liver homogenates were determined by HPLC under anaerobic conditions, because TQH2 easily autoxidizes to TQ under aerobic conditions. The viable hepatocytes were used for the determination without homogenization. The hepatocytes contained 3.1, ND and 5.0, 3.1-9.0, and 31.3-63.2 nmol of TQH2, TQ and Toc/g liver, respectively. However, TQH2 was not detected in liver homogenates because endogeneous TQH2 autoxidizes to TQ during preparation of homogenates under aerobic conditions. The homogenates contained 2.0-23.5 and 36.5-54.9 nmol of TQ and Toc/g liver, respectively. Addition of TQ showed that TQ was reduced and converted into TQH2 in isolated hepatocytes. The TQH2 formation from TQ was also observed in liver homogenates in the presence of either NADPH or NADH. The formation was further analysed and confirmed by HPLC and mass spectrometry. The formation of TQH2 was also found to occur in mitochondria, microsomes and cytosol. The specific activity of NADPH-dependent TQ reductase activity was in the order of mitochondria greater than or equal to microsomes greater than cytosol. Furthermore, NADPH-cytochrome P450 reductase was found to catalyse TQH2 formation from TQ.

Topics: alpha-Tocopherol; Animals; Liver; Male; Mitochondria, Liver; NADH Dehydrogenase; Oxidation-Reduction; Oxidoreductases; Rats; Rats, Inbred Strains; Subcellular Fractions; Vitamin E

The antioxidant effect of alpha-tocopherolquinone and alpha-tocopherolhydroquinone was studied in liposomes and rat liver submitochondrial particles. Both alpha-tocopherolquinone and alpha-tocopherolhydroquinone inhibit lipid peroxidation induced by ascorbate/Fe2+ in liposomes and by cumene hydroperoxide in submitochondrial particles. Alpha-tocopherolhydroquinone is much more effective than alpha-tocopherolquinone in inhibiting lipid peroxidation. Submitochondrial particles, depleted of ubiquinones and reincorporated with alpha-tocopherolquinone, are protected from lipid peroxidation only in the presence of succinate. Alpha-tocopherolquinone cannot replace endogenous ubiquinones in the respiratory chain function, nevertheless it can be reduced by the mitochondrial respiratory chain substrates, presumably through the reduced ubiquinones.

Topics: alpha-Tocopherol; Animals; Ascorbic Acid; Benzene Derivatives; Cattle; Electron Transport; Ferrous Compounds; Lipid Peroxides; Liposomes; Malondialdehyde; Mitochondria, Liver; Oxidation-Reduction; Rats; Submitochondrial Particles; Succinates; Succinic Acid; Ubiquinone; Vitamin E

Topics: alpha-Tocopherol; Animals; Humans; Liver; Rats; Vitamin E

Both alpha-tocopherolquinol and alpha-tocopherolquinone were found in 56 of 93 strains of microorganisms examined. Organisms that contained these compounds included the single example of a eucaryotic alga, a Euglena, and a cyanobacterium (blue-green alga), 22 of 32 genera of bacteria, and 9 genera of yeasts. In the bacteria and yeasts the levels of quinone and hydroquinone were nearly equal and averaged about 3 nmol of each compound g-1 of packed cells. Included among the bacteria that contained these compounds were three examples from the newly proposed kingdom of Archaebacteriae. Those microorganisms that did not contain alpha-tocopherolquinol or alpha-tocopherolquinone tended to fall into two groups. One group consisted of gram-positive, anaerobic or facultative bacteria with a low content of guanine and cytosine, and the second group encompassed all of the filamentous microorganisms studied. No metabolic function is known for alpha-tocopherolquinol or its quinone other than as a cofactor in the biohydrogenation of unsaturated fatty acids that can be carried out by only a few organisms.

Topics: alpha-Tocopherol; Bacteria; Cyanobacteria; Euglena gracilis; Eukaryota; Fungi; Vitamin E; Yeasts