Showing papers on "Ascorbic acid published in 1991"

Ascorbic acid protects against endogenous oxidative DNA damage in human sperm.

Abstract: Damage to the DNA of germ cells can lead to mutation, which may result in birth defects, genetic diseases, and cancer. The very high endogenous rate of oxidative DNA damage and the importance of dietary ascorbic acid (AA) in preventing this damage has prompted an examination of these factors in human sperm DNA. The oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (8-oxo-7,8-dihydro-2'-deoxyguanosine; oxo8dG), 1 of approximately 20 major products of oxidative damage to DNA, was measured in DNA isolated from human sperm provided by healthy subjects and compared to the seminal fluid AA levels. This relationship was studied in two groups. In a group of 24 free-living individuals 20-50 years old high levels of oxo8dG were correlated with low seminal plasma AA. The endogenous level of oxo8dG in this group was 13 fmol per microgram of DNA or approximately 25,000 adducts per sperm cell. The second group of individuals was maintained on a controlled diet that varied only in AA content. When dietary AA was decreased from 250 to 5 mg/day, the seminal fluid AA decreased by half and the level of oxo8dG in sperm DNA increased 91%. Repletion of dietary AA for 28 days (from 5 mg/day to 250 or 60 mg/day) caused a doubling in seminal fluid AA and reduced oxo8dG by 36%. These results indicate that dietary AA protects human sperm from endogenous oxidative DNA damage that could affect sperm quality and increase risk of genetic defects, particularly in populations with low AA such as smokers.

Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol

Abstract: The temporal disappearance of natural antioxidants associated with human low density lipoprotein (LDL) in relation to the appearance of various classes of lipid hydroperoxides was investigated under three types of oxidizing conditions. Freshly isolated LDL from plasma of healthy subjects was free of detectable amounts of lipid hydroperoxides as measured by HPLC postcolumn chemiluminescence detection. Exposure of such LDL to a mild, constant flux of aqueous peroxyl radicals led to rapid and complete oxidation of ubiquinol-10, followed by slower partial depletion of lycopene, beta-carotene, and alpha-tocopherol. After an initial lag period of complete inhibition of detectable lipid peroxidation, formation of hydroperoxides of cholesterol esters, triglycerides, and phospholipids was observed. The onset of detectable lipid peroxidation corresponded closely with the completion of ubiquinol-10 consumption. However, small amounts of ascorbate, present as a contaminant in the LDL preparation, rather than ubiquinol-10 itself were responsible for the initial lag period. Thus, complete consumption of ubiquinol-10 was preceded by that of ascorbate, and exposure of ascorbate-free LDL to aqueous peroxyl radicals resulted in immediate formation of detectable amounts of lipid hydroperoxides. The rate of radical-mediated formation of lipid hydroperoxides in ascorbate-free LDL was low as long as ubiquinol-10 was present, but increased rapidly after its consumption, even though more than 80% and 95% of endogenous carotenoids and alpha-tocopherol, respectively, were still present. Qualitatively similar results were obtained when peroxyl radicals were generated within LDL or when the lipoprotein was exposed to oxidants produced by activated human polymorphonuclear leukocytes. LDL oxidation was reduced significantly by supplementing the lipoprotein preparation with physiological amounts of either ascorbate or ubiquinol-10. Our data show that ubiquinol-10 is much more efficient in inhibiting LDL oxidation than either lycopene, beta-carotene, or alpha-tocopherol.

Handbook of Vitamins

Abstract: Vitamin A: Nutritional Aspects of Retinoids and Carotenoids, A.C. Ross and E.H. Harrison Vitamin D, A.W. Norman and H.L. Henry Vitamin K, J.W. Suttie Vitamin E, M.G. Traber Bioorganic Mechanisms Important to Coenzyme Functions, D.B. McCormick Niacin, J.B. Kirkland Riboflavin (Vitamin B2), R.S. Rivlin Thiamine, C.J. Bates Pantothenic Acid, R.B. Rucker and K. Bauerly Vitamin B6, S. Dakshinamurti and K. Dakshinamurti Biotin, D.M. Mock Folic Acid, L.B. Bailey Vitamin B12, R. Green and J.W. Miller Choline, T.A. Garrow Ascorbic Acid, C.S. Johnston, F.M. Steinberg, and R.B. Rucker Vitamin-Dependent Modifications of Chromatin: Epigenetic Events and Genomic Stability, J.B. Kirkland, J. Zempleni, L.K. Buckles, and J.K. Christman Accelerator Mass Spectrometry in the Study of Vitamins and Mineral Metabolism in Humans, F. Fonseca de Moura, B.J. Burri, and A.J. Clifford Dietary Reference Intakes for Vitamins, S.P. Murphy and S.I. Barr Index

Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase.

Abstract: Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia.

Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective effects of ascorbic acid.

Abstract: Cigarette smoke (CS) is known to contain a large number of oxidants. In order to assess the oxidative effects of CS on biological fluids, we exposed human blood plasma to filtered (gas phase) and unfiltered (whole) CS, and determined the rate of utilization of endogenous antioxidants in relation to the appearance of lipid hydroperoxides. Lipid peroxidation was measured with a specific and sensitive assay that can detect lipid hydroperoxides at plasma levels as low as 10 nM. We found that exposure of plasma to the gas phase of CS, but not to whole CS, induces lipid peroxidation once endogenous ascorbic acid has been oxidized completely. In addition, CS exposure caused oxidation of plasma protein thiols and albumin-bound bilirubin, whereas uric acid and alpha-tocopherol were not consumed at significant rates. In plasma exposed to the gas phase of CS, low-density lipoprotein exhibited slightly increased electrophoretic mobility, but there was no apparent degradation of apolipoprotein B. Our results support the concept of an increased vitamin C utilization in smokers, and suggest that lipid peroxidation induced by oxidants present in the gas phase of CS leads to potentially atherogenic changes in lipoproteins.

Copper-ion-dependent damage to the bases in DNA in the presence of hydrogen peroxide.

Abstract: Mixtures of Cu2+ and H2O2 at pH 7.4 caused damage to the bases in DNA greater than that caused by mixtures of Fe3+ and H2O2. Addition of ascorbic acid to the Cu2+/H2O2 system caused a very large increase in base damage, much greater than that produced by the Fe3+/H2O2/ascorbic acid system. The products of base damage in the presence of Cu2+ were typical products that have been shown to result from attack of hydroxyl radicals upon the DNA bases. Cytosine glycol, thymine glycol, 8-hydroxyadenine and especially 8-hydroxyguanine were the major products in both the Cu2+/H2O2 and the Cu2+/H2O2/ascorbic acid systems. Base damage in DNA by these systems was inhibited by the chelating agents EDTA and nitrilotriacetic acid and by catalase, but not by superoxide dismutase, nor by the hydroxyl-radical scavenger mannitol. It is proposed that Cu2+ ions bound to the DNA react with H2O2 and ascorbic acid to generate hydroxyl radicals, which then immediately attack the DNA bases in a site-specific manner. A hypoxanthine/xanthine oxidase system also caused damage to the DNA bases in the presence of Cu2+ ions. This was inhibited by superoxide dismutase and catalase. The high activity of Cu2+ ions, when compared with Fe3- ions, in causing hydroxyl-radical-dependent damage to DNA and to other biomolecules, means that the availability of Cu2+ ions in vivo must be carefully controlled.

Acute Helicobacter pylori infection: clinical features, local and systemic immune response, gastric mucosal histology, and gastric juice ascorbic acid concentrations.

Abstract: The symptomatology of a case of acute infection with Helicobacter pylori is described, together with the accompanying changes in gastric mucosal histology, local and systemic humoral immune response, and gastric ascorbic acid concentration. The patient was an endoscopist, previously negative for the carbon-14 urea breath test, who had a week of epigastric pain and then became asymptomatic. H pylori was detected by culture of antral biopsy specimens and was still present after 74 days. Five days after infection the histological findings showed acute neutrophilic gastritis; by day 74 changes of chronic gastritis were evident. The patient seroconverted by IgG enzyme linked immunosorbent assay by day 74, but a mucosal IgM and IgA response was evident as early as day 14. Infection was accompanied by a transient hypochlorhydria but a sustained fall in gastric juice ascorbic acid concentration.

Drug antioxidant effects-a basis for drug selection

Abstract: A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology of more than 50 human diseases. Radicals and other reactive oxygen species are formed constantly in the human body, both by deliberate synthesis (e.g. by activated phagocytes) and by chemical side-reactions. They are removed by enzymic and nonenzymic antioxidant defence systems. Oxidative stress, occurring when antioxidant defences are inadequate, can damage lipids, proteins, carbohydrates and DNA. A few clinical conditions are caused by oxidative stress, but more often the stress results from the disease. Sometimes it then makes a significant contribution to the disease pathology, and sometimes it does not. Several antioxidants are available for therapeutic use. They include molecules naturally present in the body [superoxide dismutase (SOD), alpha-tocopherol, glutathione and its precursors, ascorbic acid, adenosine, lactoferrin and carotenoids] as well as synthetic antioxidants [such as thiols, ebselen (PZ51), xanthine oxidase inhibitors, inhibitors of phagocyte function, iron ion chelators and probucol]. The therapeutic efficacy of SOD, alpha-tocopherol and ascorbic acid in the treatment of human disease is generally unimpressive to date although dietary deficiencies of the last two molecules should certainly be avoided. Xanthine oxidase inhibitors may be of limited relevance as antioxidants for human use. Exciting preliminary results with probucol (antiatherosclerosis), ebselen (anti-inflammatory), and iron ion chelators (in thalassaemia, leukaemia, malaria, stroke, traumatic brain injury and haemorrhagic shock) need to be confirmed by controlled clinical trials. Clinical testing of N-acetylcysteine in HIV-1-positive subjects may also be merited. A few drugs already in clinical use may have some antioxidant properties, but this ability is not widespread and drug-derived radicals may occasionally cause significant damage.

Glutathione deficiency decreases tissue ascorbate levels in newborn rats: ascorbate spares glutathione and protects

Abstract: Glutathione deficiency in newborn rats, produced by administration of L-buthionine-(S,R)-sulfoximine, a transition-state inactivator of gamma-glutamylcysteine synthetase, decreases ascorbate levels of kidney, liver, brain, and lung. These tissues, especially their mitochondria, undergo severe damage and the animals die within a few days. When glutathione levels are markedly decreased, ascorbate levels decrease leading to formation of dehydroascorbate, which is degraded. Ascorbate has high antioxidant activity, but it (and other antioxidants such as alpha-tocopherol) must be maintained in reduced forms. These studies show in vivo that an important function of glutathione is to maintain tissue ascorbate. Administration of large doses of ascorbate (but not of dehydroascorbate) to buthionine sulfoximine-treated newborn rats decreases mortality, leads to normal levels of ascorbate, and spares glutathione. Newborn rats given lower doses of buthionine sulfoximine develop cataracts that, as shown previously, can be prevented by giving glutathione monoester; as found here, such cataracts can be partially prevented by administration of high doses of ascorbate or dehydroascorbate. Ascorbate spares glutathione indicating that these compounds have similar antioxidant actions. Ascorbate may have reductive functions that are not efficiently performed by glutathione. Although glutathione normally functions to maintain ascorbate, alpha-tocopherol, and other cellular components in reduced states, ascorbate can serve as an essential antioxidant in the presence of severe glutathione deficiency.

Increased blood antioxidant systems of runners in response to training load.

Abstract: 1. Blood antioxidants were measured in venous blood samples from 20 runners and six sedentary individuals. All subjects were male, between 20 and 40 years old, and in steady state with respect to body weight and physical activity patterns. Dietary analysis was undertaken using a 7-day weighed food intake. Correlations were sought between antioxidants in blood and (1) weekly training distance and (2) maximum oxygen uptake. In addition, 12 runners could be classified into two groups undertaking either low (range 16-43 km, n = 6) or high (80-147 km, n = 6) weekly training. 2. Body weight (range 55.3-90.0 kg) and percentage body fat (range 7-19%) both showed negative correlations with the weekly training distance (both P less than 0.001). Energy intake and maximum oxygen uptake were both correlated with the weekly training distance (both P less than 0.001). 3. Plasma creatine kinase activity, an indicator of muscle damage, was significantly correlated with the weekly training distance (P less than 0.01), whereas the plasma concentration of thiobarbituric acid-reactive substances, an indicator of free-radical-mediated lipid peroxidation, decreased with increased maximum oxygen uptake (P less than 0.01). 4. Erythrocyte alpha-tocopherol content was greater in the two running groups (P less than 0.05) compared with the sedentary group, and lymphocyte ascorbic acid concentration was significantly elevated in the high-training group (P less than 0.01) compared with the low-training group. 5. Erythrocyte activities of the antioxidant enzymes, glutathione peroxidase and catalase, were significantly and positively correlated with the weekly training distance (P less than 0.01 and P less than 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

High correlation between pentosidine protein crosslinks and pigmentation implicates ascorbate oxidation in human lens senescence and cataractogenesis

Abstract: Pentosidine is a recently discovered protein crosslink, involving lysine and arginine residues linked together in an imidazo [4,5,6] pyridinium ring formed by a 5-carbon sugar during nonenzymatic browning (Maillard reaction). The presence of high ascorbate levels in the human lens and its ability to undergo nonenzymatic browning led us to investigate pentosidine formation in the aging human lens. Incubation of lens crystallins with ascorbate and its oxidation products dehydroascorbate and 2,3-diketogulonate leads progressively to the formation of pentosidine crosslinks in the presence of oxygen. Under nitrogen, however, pentosidine forms only from 2,3-diketogulonate or xylosone, a degradation product of 2,3-diketogulonate. A high correlation between pentosidine crosslinks and the degree of lens pigmentation is noted in cataractous lenses. Pentosidine is found to be primarily associated with alpha-crystallin fractions of 300-5000 kDa. These results suggest that redox imbalance in cellular senescent systems such as the ocular lens may lead to irreversible ascorbate oxidation and protein crosslinking by xylosone. This mechanism may play an important role in the pathogenesis of "brunescent" cataracts.

Interferences in current methods for measurements of creatinine

Abstract: We measured the interference of carbonyl compounds, drugs, and other substances in human serum on the determination of creatinine by the two-point, fixed-time kinetic modification of the Jaffe reaction as well as by four enzymatic methods. We added known concentrations of the interfering substances to a solution of creatinine in water. For bilirubin, we used both pooled normal sera with added bilirubin and icteric patient sera. The magnitude of interferences varies widely from method to method. Carbonyl compounds, dopamine, cephalosporines, and bilirubin interfere with the Jaffe reaction. Bilirubin, creatine, dopamine, ascorbic acid, and sarcosine interfere with the enzymatic methods. We conclude that the elimination of interferences in the determination of creatinine has still not been achieved.

Vitamin C: newer insights into its biochemical functions.

Abstract: Ever since the discovery of vitamin C (ascorbic acid), scientists have been intrigued as to how ascorbic acid deficiency can lead to the diverse symptoms exhibited in scurvy. Only in recent years has it been appreciated that ascorbic acid has important functions in many cellular reactions and processes in addition to its role in collagen synthesis. The few such reactions that are understood at the molecular level make it apparent that ascorbic acid does not directly participate in enzyme-catalyzed conversion of substrate to product. Instead, the vitamin regenerates prosthetic metal ions in these enzymes in their required reduced forms. This is in agreement with other antioxidant functions of vitamin C, e.g., scavenging of free radicals. Ascorbate and other antioxidant nutrients are presumed to play a pivotal role in minimizing the damage from oxidative products, including free radicals. This protective function is twofold: the already-oxidized groups in prosthetic centers of enzymes are reduced and the oxidants and free radicals are removed.