dinoprost and hydroxyoctadecadienoic-acid

Crystalline silica (SiO

Topics: Air Pollutants; Animals; Biomarkers; Bronchoalveolar Lavage Fluid; Carcinogens, Environmental; Dinoprost; Disease Models, Animal; Fatty Acids, Unsaturated; Heme Oxygenase-1; Instillation, Drug; Kinetics; Lipid Peroxidation; Lung; Male; Oxidative Stress; Particle Size; Particulate Matter; Rats, Wistar; Respiratory Mucosa; Silicon Dioxide; Silicosis; Trachea

Free radicals and lipid peroxidation are thought to be related to the vasospasm generation after subarachnoid hemorrhage (SAH). Plasma platelet-activating factor-acetyl hydrolase (PAF-AH) degrades phospholipids with an oxidatively modified fatty acyl chain.. To compare plasma PAF-AH activity and free forms of biomarker of lipid peroxidation in cerebrospinal fluid (CSF) between patients with and without symptomatic vasospasm (SVS) after SAH.. The identification of PAF-AH in CSF was performed by Western blotting. The genotype at position 279 of the plasma PAF-AH gene was determined. The activities of PAF-AH and the levels of free 8-iso-prostaglandin F2α (free isoPs), free hydroxyoctadecadienoic acid (free HODE), and free hydroxyeicosatetraenoic acid (free HETE) in CSF were measured.. The PAF-AH in CSF was confirmed to be only the plasma type. The genotype of the plasma PAF-AH was not different between patients with and without SVS. Free isoPs, free HODE, and free HETE showed higher values in patients without SVS in 0 to 4 days and 5 to 9 days after SAH. The PAF-AH activity also was higher in patients without SVS in 0 to 4 days and 5 to 9 days after SAH. The associations between PAF-AH activity and free isoPs, and between PAF-AH activity and free HODE were significant.. Oxidized lipids of lipoproteins and blood cell membranes produced by reactive oxygen species in CSF when SAH occurs may be the main source of lipid peroxidation. Plasma PAF-AH can hydrolyze oxidized phospholipids, and may attenuate the spreading of lipid peroxidation and participate in defense mechanisms against vasospasm after SAH.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Aged; Biomarkers; Dinoprost; Enzyme Activation; Fatty Acids, Unsaturated; Female; Genotype; Hemoglobins; Humans; Hydroxyeicosatetraenoic Acids; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Phospholipids; Subarachnoid Hemorrhage; Vasospasm, Intracranial

It is widely accepted that oxidative stress is involved in the pathogenesis of Down syndrome, but the effectiveness of antioxidant treatment remains inconclusive. We tested whether chronic administration of α-tocopherol ameliorates the cognitive deficits exhibited by Ts65Dn mice, a mouse model of Down syndrome. α-Tocopherol was administered to pregnant Ts65Dn females, from the day of conception throughout the pregnancy, and to pups over their entire lifetime, from birth to the end of the behavioral testing period. Cognitive deficits were confirmed for Ts65Dn mice fed a control diet, revealing reduced anxiety or regardlessness in the elevated-plus maze task test and spatial learning deficits in the Morris water maze test. However, supplementation with α-tocopherol attenuated both cognitive impairments. In addition, we found that levels of 8-iso-prostaglandin F(2α) in brain tissue and hydroxyoctadecadienoic acid and 7-hydroxycholesterol in the plasma of Ts65Dn mice were higher than those of control mice. Supplementation with α-tocopherol decreased levels of lipid peroxidation products in Ts65Dn mice. Furthermore, we found out that α-tocopherol improved hypocellularity in the hippocampal dentate gyrus of Ts65Dn mice. These results imply that α-tocopherol supplementation from an early stage may be an effective treatment for the cognitive deficits associated with Down syndrome.

Topics: alpha-Tocopherol; Animals; Animals, Newborn; Brain; Cognition Disorders; Dinoprost; Disease Models, Animal; Down Syndrome; Fatty Acids, Unsaturated; Female; Free Radicals; Hippocampus; Hydroxycholesterols; Lipid Peroxidation; Maze Learning; Mice; Mice, Neurologic Mutants; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Space Perception

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

The possible involvement of oxidative stress in hepatitis C virus (HCV)-induced liver damage and hepatocarcinogenesis has been reported. We have recently developed a novel method to measure total hydroxyoctadecadienoic acid (tHODE) and have proposed its usefulness as a biomarker for lipid peroxidation. The present study was undertaken to evaluate oxidative stress in HCV-infected liver diseases by several potential oxidative stress markers including tHODE and further to validate the biomarkers for evaluating the efficacy of iron reduction therapy.. Total hydroxyoctadecadienoic acid, total 8-iso-prostagrandin F(2alpha) (t8-iso-PGF(2alpha)), selenoprotein P and other antioxidant compounds were measured in the plasma and erythrocytes obtained from 42 healthy controls and 78 HCV patients. Plasma levels of biomarkers and antioxidants were also assessed during the iron reduction therapy for 16 weeks in 12 HCV patients.. The concentrations of tHODE in the plasma and erythrocytes and t8-iso-PGF(2alpha) in the plasma of chronic HCV-infected patients were significantly higher than those of healthy controls. Plasma levels of vitamin E and vitamin C of HCV-infected patients were lower than those of the controls. Furthermore, the plasma tHODE significantly correlated with serum aminotransferases and type IV collagen-7S domain in chronic HCV-infected patients. During the iron reduction therapy, the plasma levels of tHODE but not t8-iso-PGF(2alpha) decreased and inversely its stereo-isomer ratio (ZE/EE) increased in parallel with the decreases of serum alanine aminotransferase, ferritin and alpha-fetoprotein.. The levels of tHODE in chronic HCV-infected patients can be a useful biomarker for the evaluation of oxidative stress in chronic hepatitis C.

Topics: Aged; Antioxidants; Biomarkers; Dinoprost; Fatty Acids, Unsaturated; Female; Ferritins; Hemoglobins; Hepacivirus; Hepatitis C; Humans; Liver; Liver Cirrhosis; Male; Middle Aged; Oxidative Stress; Phlebotomy; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; RNA, Viral; Time Factors; Treatment Outcome

To assess the antioxidative role of vitamin E (VE) in a mouse model of severe VE deficiency by using biomarkers, alpha-tocopherol transfer protein (alpha-TTP(-/-))-knockout mice were maintained on a VE-deficient diet for 28 weeks [KO group, n = 6]. Wild-type C57BL/6 mice were maintained on a diet containing 0.002% alpha-tocopherol [WT group, n = 6]. The animals were housed individually in a metabolic cage from the age of 9 weeks (Week 0) to 27 weeks. Urine was collected every week, and the levels of total hydroxyoctadecadienoic acid (tHODE), 7-hydroxycholesterol (t7-OHCh), and 8-iso-prostaglandin F(2alpha)(t8-isoPGF(2alpha)), which are biomarkers for lipid peroxidation, were measured by gas chromatography (GC)-mass spectrometry. From the age of 21 weeks (Week 12), three mice in each group were provided drinking water containing the water-soluble radical initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) until the end of the study (Week 19). Blood and tissue samples were collected, and the levels of the abovementioned biomarkers therein were assessed. AIPH consumption clearly elevated the plasma and erythrocyte levels of tHODE and t8-isoPGF(2alpha) in both the WT and KO groups except for the erythrocyte level of tHODE in the WT group. Furthermore, this elevation was more prominent in the KO group than in the WT group. Interestingly, AIPH consumption reduced the stereoisomer ratio of HODE (ZE/EE), which is reflective of the efficacy of a compound as an antioxidant in vivo; this suggests that free radical-mediated oxidation reduces the antioxidant capacity in vivo. The urine levels of tHODE, t7-OHCh, and t8-isoPGF(2alpha) tended to increase with AIPH consumption, but these individual levels fluctuated. It was clearly demonstrated by the proposed biomarkers that maintaining alpha-TTP(-/-) mice on a VE-deficient diet results in a severe VE deficiency and promotes lipid peroxidation.

Topics: alpha-Tocopherol; Animals; Azo Compounds; Biomarkers; Carrier Proteins; Diet; Dinoprost; Disease Models, Animal; Erythrocytes; Fatty Acids, Unsaturated; Free Radicals; Hydroxycholesterols; Imidazoles; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Time Factors; Tissue Distribution; Vitamin E Deficiency; Water Supply

To assess the role of vitamin E (VE) in age-related changes in the retinal tissues by using a mouse model of severe VE deficiency.. Pups of alpha-tocopherol transfer protein null (a-TTP(-)(/)(-)) mice were fed a VE-deficient diet for 4 or 18 months (VE (-) group). Wild-type C57BL/6 mice were fed a 0.002% alpha-tocopherol-supplemented diet (VE (+) group). In various ocular tissues, the VE levels were measured by high-performance liquid chromatography; the fatty acid composition by gas chromatography (GC); and the hydroxyoctadecadienoic acid and 8-iso-prostaglandin F(2)(alpha) levels, which are biomarkers for lipid peroxidation, by GC-mass spectrometry. The retinal structure was assessed by light, electron, and fluorescence microscopy.. The alpha-tocopherol level in the retinas obtained from 4-month-old VE (-) animals was 71-fold lower than that in the retinas obtained from the VE (+) group. In addition, gamma-tocopherol was not detected; thus, the VE (-) group demonstrated a more severe VE deficiency than ever reported. In this group, the concentration of n-3 polyunsaturated fatty acids decreased (0.3- to 0.9-fold), whereas that of other classes of fatty acids was unchanged or increased. At 18 months of age, the number of the outer nuclear layer (ONL) nuclei was observed to be 17% lower in the VE (-) than in the VE (+) group (P < 0.05). Electron microscopy revealed larger amounts of matrix between the ONL nuclei indicating the Müller cell hypertrophy, greatly expanded rod outer segment discs, and a larger number of inclusion bodies in the retinal pigment epithelium (RPE; P < 0.05) in the VE (-) group. Fluorescence microscopy revealed that the autofluorescence signal was increased in the RPE layer in this group. When the observations of the 18-month-old animals were compared to those of the 4-month-old animals, the hydroxyoctadecadienoic acid and 8-iso-prostaglandin F(2)(alpha) levels were found to be increased in the retina and RPE obtained from both the VE (-) and VE (+) groups; however, the age-related increases were more remarkable in the VE (-) group (2.6- to 43.5-fold) than in the VE (+) group (0.8- to 8.7-fold).. The combined use of a-TTP(-)(/)(-) mice and a VE-deficient diet leads to a severe deficiency of VE, enhances lipid peroxidation in the retina, and accelerates degenerative damage of the retina with age.

Topics: Animals; Carrier Proteins; Chromatography, Gas; Chromatography, High Pressure Liquid; Diet; Dinoprost; Fatty Acids; Fatty Acids, Unsaturated; Gene Silencing; Lipid Peroxidation; Macular Degeneration; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Fluorescence; Pigment Epithelium of Eye; Retina; Vitamin E; Vitamin E Deficiency

Exposure to excessive light induces retinal photoreceptor cell damage, which may involve lipid peroxidation. Morphological changes and the detection of internucleosomal DNA fragmentation confirmed the retinal damage caused by exposure of the retina of Balb/c mice to white fluorescent light (5000 lux, 2 h). The total amounts of hydroxyoctadecadienoic acid (tHODE) and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) in the retinas obtained from light-exposed mice were assessed after reduction and saponification. In this method, both the free and ester forms of hydroperoxides, hydroxides, and ketones of linoleic acid are measured as tHODE by gas chromatography-mass spectrometry (GC-MS) analysis. When compared with controls, a significant increase in the concentrations of tHODE and 8-iso-PGF2alpha was observed 24 h after light exposure. Furthermore, the stereoisomeric ratio (Z,E)-HODE/(E,E)-HODE decreased after light exposure, suggesting the involvement of free-radical-mediated peroxidation. By the immunohistochemical technique, it was confirmed that 8-iso-PGF2alpha increased in the inner plexiform layer (IPL), outer plexiform layer (OPL), rod outer segment, and choroidal layer, while 13-HODE increased in the OPL and rod inner segment after light exposure. These results demonstrate that tHODE and 8-iso-PGF2alpha assessed by the present method are appropriate biomarkers responding to retinal photooxidative stress in vivo.

Topics: Animals; Biomarkers; Dinoprost; Fatty Acids, Unsaturated; Light; Lipid Peroxidation; Male; Mice; Mice, Inbred BALB C; Oxidative Stress; Retina; Stereoisomerism

The relevance of oxidative stress in mice fed a choline-deficient diet (CDD) was investigated in relation to the oxidative stress marker, hydroxyoctadecadienoic acid (HODE) in comparison with F2-isoprostanes. Further, the protective effects of antioxidants against oxidative damage were assessed by using HODE.. We recently proposed total HODE as a biomarker for oxidative stress in vivo. Biological samples such as plasma, urine, and tissues were first reduced and then saponified to convert various oxidation products of linoleates to HODE. In the present study, this method was applied to measure oxidative damage in mice induced by CDD for 1 mo.. CDD, when compared with choline-controlled diet (CCD), increased liver weight and fatty acid accumulation but the increase in body weight was less significant. Remarkable increases in HODE and 8-iso-prostaglandin F(2alpha) in liver and plasma were observed when mice were fed with the CDD for 1 mo compared with the CCD. The HODE level was about two to three orders higher than the F2-isoprostane level. This increase was decreased to the level of the CCD when alpha-tocopherol or 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran, a potent synthetic antioxidant, was mixed with the CDD. The stereoisomer ratio of HODE (9-and-13 (Z,E)-HODE/9-and-13 (E,E)-HODE) was decreased by CDD compared with CCD, which was spared by the addition of alpha-tocopherol and 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran. However, the increase in plasma glutamic-pyruvic transaminase and fatty acids in liver induced by the CDD was not recovered by any antioxidant.. This study clearly demonstrated that oxidative stress was involved in fatty liver formation induced by the CDD and that HODE was a good biomarker for an oxidative stress in vivo.

Topics: Animals; Antioxidants; Benzofurans; Biomarkers; Choline; Choline Deficiency; Chromatography, High Pressure Liquid; Dinoprost; Fatty Acids, Unsaturated; Fatty Liver; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Organ Size; Oxidation-Reduction; Oxidative Stress; Random Allocation; Specific Pathogen-Free Organisms

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

An improved method for the measurement of lipid peroxidation in vivo has been recently developed, where total hydroxyoctadecadienoic acid (HODE) and 7-hydroxycholesterol (FCOH) were determined by GC/MS analysis from physiological samples after reduction with sodium borohydride and saponification by potassium hydroxide. In this method, both free and ester forms of hydroperoxides and ketones as well as hydroxides of linoleic acid and cholesterol are measured as HODE and FCOH, respectively. The ratio of stereo-isomer, (Z, E)-HODE/(E, E)-HODE, could be also measured. In the present study, in order to examine the effect of continuous, slow flux of free radicals in vivo, a water-soluble radical generator was administered to rats and mice and the amounts of HODE and 8-isoprostane in plasma and liver were measured. It was found that the administration of free radical-generating azo compound increased the level of HODE and decreased the (Z, E)-HODE/(E, E)-HODE ratio in both plasma and liver. The level of HODE was much higher than 8-isoprostane.

Topics: Amidines; Animals; Azo Compounds; Biomarkers; Dinoprost; Drinking; Fatty Acids, Unsaturated; Free Radicals; Gas Chromatography-Mass Spectrometry; Hydroxycholesterols; Imidazoles; Lipid Peroxidation; Liver; Male; Mice; Rats; Specific Pathogen-Free Organisms

It is important to assess the oxidative injury in vivo accurately and inclusively, as the oxidative stress induced by various oxidants in a random and destructive fashion is considered to play an important role in the pathophysiology of a number of human disorders and diseases. We have developed an improved method for the measurement of lipid peroxidation in vivo, where total hydroxyoctadecadienoic acids (HODE) and 7-hydroxycholesterol (FCOH) were determined by GC/MS analysis from physiological samples after reduction with sodium borohydride and saponification by potassium hydroxide. In this method, both free and ester forms of hydroperoxides and ketones as well as hydroxides of linoleate and cholesterol are measured as HODE and FCOH, respectively. The ratio of stereo-isomers, (E,E)-HODE/(E,Z)-HODE, could be also measured. The plasma concentrations of total HODE were obtained as 76.5, 666 and 2225 nM for human, rat and mouse, respectively. It was found that HODE and FCOH could be measured satisfactorily by the present method from plasma, erythrocyte and urine of humans and experimental animals. It was also found that HODE in urine arose from both free and ester forms, while 8-iso-prostaglandin F2alpha was present primarily as a free acid form. As the concentrations of HODE were much higher than 8-iso-prostaglandin F2alpha, HODE may well be used as a good oxidative marker in vivo.

Topics: Adult; Biomarkers; Chromatography, Gas; Dinoprost; Fatty Acids, Unsaturated; Humans; Hydroxycholesterols; Lipid Peroxidation; Male; Mass Spectrometry; Molecular Structure; Oxidation-Reduction; Oxidative Stress