ubiquinone and hydroxyoctadecadienoic-acid

It has been hypothesized that oxidative stress plays a key role in aging. In order to elucidate the role of the antioxidant network - including alpha-tocopherol (alphaT) and alphaT transfer protein - in aging in vivo, alpha-tocopherol transfer protein knockout (alphaTTP(-/-)) mice were fed a vitamin-E-depleted diet, and wild-type (WT) mice were fed a diet containing 0.002 wt.% alphaT from the age of 3 months to 1 1/2 years. The lipid oxidation markers total hydroxyoctadecadienoic acid (tHODE) and 8-iso-prostaglandin F(2)alpha, and antioxidant levels in the blood, liver and brain were measured at 3, 6, 12 and 18 months. tHODE levels in the plasma of alphaTTP(-/-) mice were elevated at 6 months compared to 3 months, and were significantly higher those in WT mice, although they decreased thereafter. On the other hand, tHODE levels in the liver and brain were constantly higher in alphaTTP(-/-) mice than in WT mice. Motor activities decreased with aging in both mouse types; however, those in the alphaTTP(-/-) mice were lower than those in the WT mice. It is intriguing to note that motor activities were significantly correlated with the stereoisomer ratio (Z,E/E,E) of HODE, which is a measure of antioxidant capacity in vivo, in the plasma, in the liver and even in the brain, but not with other factors such as antioxidant levels. In summary, using the biomarker tHODE and its stereoisomer ratio, we demonstrated that alphaT depletion was associated with a decrease in motor function, and that this may be primarily attributable to a decrease in the total antioxidant capacity in vivo.

Topics: Aging; alpha-Tocopherol; Animals; Ascorbic Acid; Biomarkers; Brain Chemistry; Carrier Proteins; Dinoprost; Fatty Acids, Unsaturated; Female; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Oxidative Stress; Specific Pathogen-Free Organisms; Stereoisomerism; Thiobarbituric Acid Reactive Substances; Ubiquinone; Vitamin E Deficiency

Coenzyme Q (CoQ) is an endogenous enzyme cofactor that may provide protective benefits as an antioxidant. In this study, in order to determine whether the concentrations of CoQ(9) are associated with the oxidative status in vivo, the effects of dietary supplements of CoQ(9) on mice were evaluated by using a new biomarker, total hydroxyoctadecadienoic acid (tHODE). Biological samples were first reduced and then saponified to convert the various oxidation products of linoleates to tHODE. Subsequently, by using GC-MS analyses, we simultaneously determined the absolute concentration of tHODE; its stereoisomer ratio, 9- and 13-(Z,E)-HODE/9- and 13-(E,E)-HODE, which is a measure of the hydrogen donor capacity of antioxidants; and the concentration of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)). Remarkable decreases in tHODE and 8-iso-PGF(2alpha) levels were observed in the plasma, erythrocytes, liver, and brain of mice that were maintained for 1 month on an alpha-tocopherol (alphaT)-free (E-free) diet supplemented with ubiquinone-9 (Q(9); 0.04 wt.%) as compared to those of mice that were fed an E-free diet. The (Z,E/E,E) HODE ratio was increased in the plasma and erythrocytes of mice that were fed a Q(9)-fortified diet as compared to those that were fed an E-free diet. In particular, the (Z,E/E,E) HODE ratios in the plasma and brain were significantly correlated with the concentrations of ubiquinol-9 (Q(9)H(2)). Further, the liver and brain levels of tHODE and 8-iso-PGF(2alpha) were significantly correlated with the plasma and erythrocyte levels of tHODE and 8-iso-PGF(2alpha), respectively, and in some cases, also exhibited significant correlations with antioxidants. These results indicate that the plasma and erythrocyte levels of tHODE and its stereoisomeric ratio can be prominent biomarkers for the evaluation of the oxidative status and antioxidant capacity in vivo, including in the liver and brain, and that CoQ plays a major role in the in vivo antioxidant network.

Topics: Alanine Transaminase; alpha-Tocopherol; Animals; Antioxidants; Brain Chemistry; Diet; Dinoprost; Fatty Acids, Unsaturated; Lipid Peroxidation; Liver; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Stereoisomerism; Ubiquinone

We have recently proposed total hydroxyoctadecadienoic acid (HODE) as a biomarker for oxidative stress in vivo. The biological samples such as plasma, urine, and tissues were first reduced and then saponified to convert the oxidation products of linoleate to HODE. In the present study, this method was applied to measure the oxidative damage induced by the administration of carbon tetrachloride to mice and also to evaluate the capacity of antioxidant to inhibit the above damage. alpha-Tocopherol transfer protein knock out (alpha-TTP-/-) mice were used to evaluate antioxidant effect in the absence of alpha-tocopherol. The intraperitoneal administration of carbon tetrachloride to mice induced the increase in HODE in liver and plasma, which was followed by an increase in plasma glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT). F2-isoprostanes, another prevailing biomarker, were also increased similarly, but their concentration was approximately two to three orders of magnitude smaller than that of HODE. The lipophilic antioxidants such as gamma-tocopherol, gamma-tocotrienol and 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran (BO-653) were effective in suppressing the formation of HODE.

Topics: Alanine Transaminase; alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Benzofurans; Biomarkers; Carbon Tetrachloride; Carrier Proteins; Chromatography, High Pressure Liquid; Diet; Dinoprost; Fatty Acids, Unsaturated; Genotype; Injections, Intraperitoneal; Lipid Peroxidation; Lipid Peroxides; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Specific Pathogen-Free Organisms; Thiobarbituric Acid Reactive Substances; Tocotrienols; Ubiquinone; Vitamin E