Showing papers on "Ascorbic acid published in 1978"

Free radicals in cerebral ischemia.

Abstract: The possibility that cerebral ischemia may initiate a series of pathological free radical reactions within the membrane components of the CNS was investigated in the cat. The normally occurring electron transport radicals require adequate molecular oxygen for orderly transport of electrons and protons. A decrease in tissue oxygen removes the controls over the electron transport radicals, and allows them to initiate pathologic radical reactions among cell membranes such as mitochondria. Pathologic radical reactions result in multiple products, each of which may be present in too small a concentration to permit their detection at early time periods. It is possible to follow the time course, however, by the decrease of a major antioxidant as it is consumed by the pathologic radical reactions. For this reason, ascorbic acid was measured in ischemic and control brain following middle cerebral artery occlusion. There was a progressive decrease in the amount of detectable ascorbic acid ranging from 25% at 1 hour to 65% at 24 hours after occlusion. The reduction of this normally occurring antioxidant and free radical scavenger may indicate consumption of ascorbic acid in an attempt to quench pathologic free radical reactions occurring within the components of cytomembranes.

Supplemental ascorbate in the supportive treatment of cancer: Reevaluation of prolongation of survival times in terminal human cancer

Abstract: A study has been made of the survival times of 100 terminal cancer patients who were given supplemental ascorbate, usually 10 g/day, as part of their routine management and 1000 matched controls, similar patients who had received the same treatment except for the ascorbate. The two sets of patients were in part the same as those used in our earlier study [Cameron, E. & Pauling, L. (1976) Proc. Natl. Acad. Sci. USA 73, 3685-3689]. Tests confirm that the ascorbate-treated patients and the matched controls are representative subpopulations of the same population of “untreatable” patients. Survival times were measured not only from the date of “untreatability” but also from the precisely known date of first hospital attendance for the cancer that eventually reached the terminal stage. The ascorbate-treated patients were found to have a mean survival time about 300 days greater than that of the controls. Survival times greater than 1 yr after the date of untreatability were observed for 22% of the ascorbate-treated patients and for 0.4% of the controls. The mean survival time of these 22 ascorbate-treated patients is 2.4 yr after reaching the apparently terminal stage; 8 of the ascorbate-treated patients are still alive, with a mean survival time after untreatability of 3.5 yr.

Properties and physiological function of a glutathione reductase purified from spinach leaves by affinity chromatography.

Abstract: Glutathione reductase (EC 1.6.4.2) was purified from spinach (Spinacia oleracea L.) leaves by affinity chromatography on ADP-Sepharose. The purified enzyme has a specific activity of 246 enzyme units/mg protein and is homogeneous by the criterion of polyacrylamide gel electrophoresis on native and SDS-gels. The enzyme has a molecular weight of 145,000 and consists of two subunits of similar size. The pH optimum of spinach glutathione reductase is 8.5–9.0, which is related to the function it performs in the chloroplast stroma. It is specific for oxidised glutathione (GSSG) but shows a low activity with NADH as electron donor. The pH optimum for NADH-dependent GSSG reduction is lower than that for NADPH-dependent reduction. The enzyme has a low affinity for reduced glutathione (GSH) and for NADP+, but GSH-dependent NADP+ reduction is stimulated by addition of dithiothreitol. Spinach glutathione reductase is inhibited on incubation with reagents that react with thiol groups, or with heavymetal ions such as Zn2+. GSSG protects the enzyme against inhibition but NADPH does not. Pre-incubation of the enzyme with NADPH decreases its activity, so kinetic studies were performed in which the reaction was initiated by adding NADPH or enzyme. The Km for GSSG was approximately 200 μM and that for NADPH was about 3 μM. NADP+ inhibited the enzyme, assayed in the direction of GSSG reduction, competitively with respect to NADPH and non-competitively with respect to GSSG. In contrast, GSH inhibited non-competitively with respect to both NADPH and GSSG. Illuminated chloroplasts, or chloroplasts kept in the dark, contain equal activities of glutathione reductase. The kinetic properties of the enzyme (listed above) suggest that GSH/GSSG ratios in chloroplasts will be very high under both light and dark conditions. This prediction was confirmed experimentally. GSH or GSSG play no part in the light-induced activation of chloroplast fructose diphosphatase or NADP+-glyceraldehyde-3-phosphate dehydrogenase. We suggest that GSH helps to stabilise chloroplast enzymes and may also play a role in removing H2O2. Glucose-6-phosphate dehydrogenase activity may be required in chloroplasts in the dark in order to provide NADPH for glutathione reductase.

Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides

Abstract: Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca(2+) and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca(2+) is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as beta-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca(2+). Successive cycles of Ca(2+) release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca(2+)-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca(2+), mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport.

Pathology of the Vitamin C Deficiency Syndrome in Channel Catfish (Ictalurus punctatus)

Abstract: Channel catfish fingerlings fed purified diets devoid of vitamin C showed reduced growth rate, deformed spinal columns, external and internal hemorrhages, erosion of fins, dark skin color and reduced bone collagen content after 8 to 12 weeks, whereas fish fed a diet containing 30 mg/kg of vitamin C had none of these anomalies after 22 weeks. A dietary level of 30 mg of vitamin C per kg was insufficient to prevent distortion of gill filament cartilage, although 60 mg of vitamin C per kg was sufficient. Vertebral collagen percentages of 25 or below and liver ascorbic acid levels of 30 microgram/g or below appeared to be indicative of vitamin C deficiency in channel catfish fingerlings. Epidermis and dermis were almost completely healed and extensive collagen fiber formation had commenced in the somatic muscle, in experimentally inflicted wounds after 10 days in fish fed the vitamin C-free diet. Skin and muscle at the wound site were almost regenerated to normal after 10 days in fish fed 60 mg of vitamin C per kg of diet.

Activated oxygen species and oxidation of food constituents

Abstract: Activated oxygen species which may be important in initiating oxidative changes in foods include singlet oxygen, hydroxyl radical, ozone, superoxide anion (perhydroxyl radical at low pH), and hydrogen peroxide. Chemical and enzymic reactions known to occur in biological materials can generate singlet oxygen, hydroxyl radical, superoxide anion, and hydrogen peroxide. Ozone is primarily a product of photoreactions in polluted air. Reactions involving singlet oxygen, hydroxyl radical, and ozone with food constituents can ultimately yield peroxides which decompose to initiate oxidative chain reactions. Superoxide anion and hydrogen peroxide are relatively inert toward organic molecules but can decompose to produce the more reactive singlet oxygen and hydroxyl radical. Inhibition of reactions initiated by reactive oxygen species in foods should be very important in preserving the oxidative stability of foods. The generation, detection, measurement, reaction, and inhibition of reactions of active oxygen species are surveyed in this review.

Pharmacology and neurochemistry of apomorphine.

Abstract: Publisher Summary This chapter discusses the pharmacology and neurochemistry of apomorphine. Apomorphine was first employed as a powerful emetic agent. Apomorphine can be obtained by the acid-catalyzed rearrangement of morphine and by total synthesis. The hydrochloride forms colorless crystals that readily undergo superficial oxidation and assume a greenish tinge. Apomorphine solutions in water are unstable, turning green upon exposure to light and to air oxygen. Oxidation of apomorphine is much slower in acidic media. These properties of apomorphine explain the current addition of ascorbic acid to apomorphine solutions. The preparation of apomorphine by the acid-catalyzed rearrangement of morphine results in the retention of the configuration at the C6a chiral center leading to the corresponding (–)-isomer. Apomorphine has been measured in biological samples by spectrophotometric and fluorimetric methods and by fluorescence quenching after chromatographic separation. Apomorphine is metabolized by O-glucuronidation, O-methylation, and, probably, by N-demethylation. Apomorphine is methylated in vitro when incubated with rat liver soluble fraction in the presence of S-adenosylmethionine as methyl donor. This reaction is carried by the enzyme COMT.

The living state and cancer.

Abstract: The surrounding world can be divided into two parts: alive and inanimate. What makes the difference is the subtle reactivity of living systems. The difference is so great that it is reasonable to suppose that what underlies life is a specific physical state, 'the living state'. Living systems are built mainly of nucleic acids and proteins. The former are the guardians of the basic blueprint while the business of life is carried on by proteins. Proteins thus have to share the subtle reactivity of living systems. A closed-shell protein molecule, however, has no electronic mobility, and has but a low chemical reactivity. Its orbitals are occupied by electron pairs which are held firmly. The situation can be changed by taking single electrons out of the system. This unpairs electrons, leaves half-occupied orbitals with positive electron holes, making the molecules into highly reactive paramagnetic free radicals. The reactivity of the system depends on the degree of its electronic desaturation. Electrons can be taken out of protein molecules by 'electron aceptors' in 'cahrge transfer'. When life began, our globe was covered by dense water vapour. There was no light and no free oxygen. Electron acceptors could be made out of trioses by concentrating their carbon atoms as carbonyls at one end of the molecule. The resulting methylglyoxal is a weak acceptor which made a low level of development possible. When light appeared, free oxygen was generated by the energy of photons. Oxygen is a strong electron acceptor. Its appearance opened the way to the present level of development. The transfer of electrons from protein to oxygen is effected by a complex chemical mechanism which involves ascorbic acid.

Metabolic deactivation of hexavalent chromium mutagenicity.

Abstract: Hexavalent chromium compounds (sodium dichromate, potassium chromate, chromic acid, basic zinc chromate and basic lead chromate) were found to be mutagenic for his − strains of S. typhimurium by inducing both frameshifts and base-pair substitutions. However, addition of either microsomal fractions from rat liver or of human erythrocyte lysates resulted in a complete loss of mutagenicity. As confirmed by chemical analysis, reversal of mutagenicity could be ascribed to reduction of the metal to the inactive trivalent form through a simple oxido-reductive reaction. In fact, reducing agents (ascorbic acid and sodium sulfite) and metabolites (GSH, DPNH and TPNH, either directly tested or obtained by mixing G6PD with S-9 mix) prevented hexavalent chromium mutagenicity, whereas an oxidizing agent (potassium permanganate) totally inhibited reversal of mutagenicity by liver and erythrocyte preparations. Enzymic conversion appeared to be involved in deactivation processes through a large production of TPNH via the hexose monophosphate oxidative pathway and other ancillary systems. On the other hand, microsomal preparations from rat lung displayed an extremely poor inactivating effect on chromium mutagenicity, and those from rat muscle, as well as human serum or plasma, were ineffective. These findings could bear relevance for the elective localization of chromium-induced tumors in human lung and could account for the results of animal carcinogenicity tests, which generally showed the development of tumors, but only at implant sites.

Effect of Graded Levels of Supplemental Ascorbic Acid in Practical Diets Fed to Rainbow Trout (Salmo gairdneri)

Abstract: Deficiency symptoms, including anorexia, lethargy, lying prostrate at the bottom of the tank, scoliosis, and lordosis, were noted 20 wk after the start of the experiment in rainbow trout (Salmo gairdneri) held at 15 °C and fed a diet with no supplemental ascorbic acid. The apparent requirement was 40 mg/kg of supplemental ascorbic acid; however, the amount added to trout diets should be in excess of this level due to processing and storage losses and other factors. The ascorbic acid requirement for rainbow trout appears to vary with the age and rate of growth of the trout in that the requirement is higher in young fish. Ascorbic acid was noted to function in the iron metabolism of rainbow trout. Liver and spleen iron levels were correlated with the ascorbic acid level in the diet and suggest either a redistribution of iron stores due to impaired release of iron from reticuloendothelial stores or an increase in the efficiency of intestinal iron absorption. Scorbutic trout developed a gradual but progressiv...

Agents That Increase Cyclic AMP Inhibit Accumulation of cGMP and Depress Human Monocyte Locomotion

Abstract: Ascorbic acid and serotonin increased the 3′,5′-guanosine monophosphate (cGMP) content and enhanced the chemotactic responsiveness of mononuclear cells from human peripheral blood. The ionophore A23187, PGE1, and polystyrene beads increased the 3′,5′-adenosine monophosphate (cAMP) content of mononuclear cells and had no effect on basal cGMP content. A23187, PGE1, and beads caused significant increases in cAMP content in preparations of adherent cells (chiefly monocytes); PGE1 and beads also increased cAMP content in the nonadherent cells (chiefly lymphocytes). A23187 and PGE1 each inhibited mononuclear cell locomotion. The chemically unrelated agents, A23187, beads, and PGE1, that raised cAMP of monocytes inhibited the accumulation of cGMP in response to serotonin and asorbic acid. PGE1 at a concentration that caused a 349% increase in cAMP inhibited the effect of serotonin on cGMP accumulation and the amplification of chemotaxis by serotonin only 37% and 40%, respectively. In contrast A23187, which increased monocyte cAMP by only 71%, inhibited the effect of serotonin on cGMP accumulation and locomotion by 85 and 79%, respectively. Although there is no clear quantitative relationship between the increase in cAMP content and the degree of inhibition of cGMP accumulation, it is possible that the elevation of cAMP in monocytes interferes with their capacity to accumulate cGMP in response to serotonin and ascorbic acid, perhaps by increasing cGMP degradation and/or inhibiting synthesis. In any case cyclic nucleotide modulation of monocyte locomotion appears to be more closely related to intracellular cGMP content than to cAMP content.

The integumentary tapetum

Abstract: Commonly found in sympetalous plants with unitegmic and tenuinucellate ovules, the integumentary tapetum exhibits great diversity in its distribution, morphology, cytology, differentiation, and behaviour. It is separated from the nucellus and embryo sac by layers of cuticle. The thickness, uniformity and continuity of cuticle is variable not only in diverse taxa but also at different places in the same species. The cuticular layers manifest interruptions, and the embryo sac wall bears certain ingrowths in the regions of these discontinuities. Ultrastructurally, the endothelial cells show characteristics of meristematic as well as secretory cells. Sometimes they develop wall projections and even contain multivesicular bodies. Large quantities of proteins, carbohydrates, ascorbic acid and some enzymes such as oxidative enzymes, amylases, proteases are also known to occur. Besides, a deposition of callose at the onset of pollination is recorded inPetunia. Proliferation of the integumentary tapetum in some hybrids results in seed abortion. It is believed that endothelium helps in coordinating growth in the ovule, channelizes nutrition to the embryo sac, and later performs the protective function.

Degradation kinetics of ascorbic acid at high temperature and water activity

Abstract: The kinetics of ascorbic acid degradation were studied in an intermediate moisture model food system as a function of water activity (0.69-0.90) and temperature (61-105°C). The disappearance of ascorbic acid in each case followed a zero order kinetic model. Rates of ascorbic acid degradation ranged from 1.5-10.5 mg/100g solids/min, while the activation energy was in the range of 14—17 Kcal/mole. It is suggested that dissolved oxygen concentration was limiting above 92°C, resulting in a rate decrease between 92 and 105°C. Rates of ascorbic acid degradation were found to increase with increasing aw, except at 105°C, where the opposite was observed. An equation derived from the integrated zero order rate law was used to predict ascorbic acid losses during an unsteady state heating process approximating a linear temperature rise, with good results. The same equation was much less accurate (predictions were 2-4 times larger), when used to predict ascorbic acid losses during extrusion processing, most likely due to the difficulty in obtaining an accurate temperature history of the extruded product.

Determination of a non-volatile N-nitrosamine on a food matrix

Abstract: A method devised for the determination of N-nitrososarcosine, in which the N-nitrosamine in solution is denitrosated with hydrogen bromide to form volatile products that are rapidly removed and determined in a chemiluminescence analyser, has been applied successfully to the same compound on powdered corn flakes. Differentiation of N-nitrososarcosine and a number of other N-nitrosamines and N-nitrosamides from inorganic nitrite was achieved by decomposing the nitrite with acetic acid prior to the denitrosation of the N-nitroso compounds. In the presence of a secondary-amine receptor limited nitrosation can occur during the process of differentiation but this can be prevented through the use of ascorbyl palmitate. In differentiating between large amounts of nitrite and much lower levels of N-nitrososarcosine on corn flakes, using a chemiluminescence analyser, the duration of the response from the nitrite can be shortened by freeze-drying the food matrix in the presence of ascorbic acid. The spectrophotometric determination of N-nitrososarcosine as nitrosyl bromide released into solution by the action of hydrogen bromide was hindered by the presence of powdered corn flakes.

Mutagenic activation of N-hydroxy-2-acetylaminofluorene in the Salmonella test system: the role of deacetylation by liver and kidney fractions from mouse and rat.

Abstract: The Ames bacterial mutagenesis system was used to evaluate the role of the deacetylase and sulfotransferase in the mutagenic activation of N-hydroxy-2-acetylaminofluorene. The mutagenicity of N-hydroxy-2-acetylaminofluorene mediated by liver or kidney microsomes was independent of treatment of mice or rats with microsomal enzyme inducers and, at equivalent protein concentrations, was the same whether mouse liver or mouse kidney microsomes were used. N-Hydroxy-2-acetylaminofluorene mutagenesis with mouse and rat liver or kidney microsomes was completely inhibited by 0.1 mM paraoxon and partially inhibited by addition of 39-phosphoadenosine 59-phosphosulfate when rat liver 9000 x g supernatant was used. Although the rates of deacetylation of 2-acetylaminofluorene and N-hydroxy-2-acetylaminofluorene in vitro were lower in kidney microsomes than in liver microsomes of either the mouse or the rat, both reactions were also completely inhibited by 0.1 mM paraoxon. The addition of ascorbic acid (10 mM) approximately doubled the mutagenicity of N-hydroxy-2-acetylaminofluorene in the presence of mouse kidney microsomes but had no effect on the mutagenicity of N-hydroxy-2-aminofluorene in the absence of microsomal protein. Butylated hydroxytoluene (10 mM) had very little or no effect, in either the absence or presence of 10 mM ascorbic acid, on the mutagenicity of N-hydroxy-2-acetylaminofluorene with liver or kidney microsomes. Our data indicate that deacetylation is the most important step in the mutagenic activation of N-hydroxy-2-acetylaminofluorene by mouse and rat liver and kidney fractions and that the arylnitrenium ion, rather than the nitroxyl free radical, is the electrophilic species interacting with the bacterial DNA, resulting in the frameshift mutation.

Foodstuff freshness keeping agents

Abstract: of the Disclosure Foodstuff freshness keeping agent comprising a particulate composition which contains a salt of manganese (II), iron (II), cobalt (II) or nickel (II), an alkali compound and a sulfite or a deliquescent substance, and optionally ascorbic acid or its salt, thereby to absorb oxygen in the interior of package of foodstuffs and/or generate therein carbon dioxide gas.

The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by coronavirus.

Abstract: Chick embryo tracheal organ cultures showed increased resistance to infection by a coronavirus after exposure to ascorbate, while chick respiratory epithelium and allantois-on-shell preparations showed no increase in resistance to infection by an influenza virus or a paramyxovirus.

Outer-Sphere Oxidation of Ascorbic Acid

Abstract: IrCI6'- Ira*'- 478' 4070 0.10-1.00 6, 20 Ir(H,0)C15- Ir(H,0)C15- 450b 3320 0.30-1.00 6, 20 Ir(H20),C14 Ir(H,0)2C14 445' 2920 0.30-1.00 6, 20 1rBr6'- IrBr,'- 585d 3800 0.30-1.00 6. 20 Mo(kN), 3- Mo(~N),~- 388e 1280 0.10-1.00 6; 20,35 Fe(phen), - Fe(phen),- 500f 6000 0.30-1 .OO 20,35 (CN),+ (CN), Fe(bpyj?- Fe(bpi1,- 492f 4700 0.30-1.00 20,35 (CN), (CNL Fe(ph4)- Fe(phen)- 4242 3220 0.30-1 .OO 20,35 Fe(sphen),& Fe(sphen),'+ 512g 12240 0.40-1.00 6, 20 Fe(bphen),,+ Fe(bphen),'+ 515g 12500 0.40-1.00 6,20

Fluorescent light-induced chromosome damage and its prevention in mouse cells in culture.

Abstract: Twenty-hour-exposure to fluorescent light produces chromatid breaks in a line of adult mouse lung cells grown in Dulbecco-Vogt medium supplemented with fetal bovine serum. The light-induced damage appears to be enhanced by increasing the concentration of oxygen in the gas phase of the culture. The effective wavelength(s) of light is in the visible range between 400 and 450 nm andis probably the mercury emission peak at 405 or 436 nm. Addition of catalase or glutathione with ascorbic acid to the culture medium reduced the number of chromatid breaks to a level not significantly different from that in the shielded cultures. It thus appears that the production of H2O2 in the culture medium or in the cell is responsible for the chromatid breaks. Most of the chromosomal abnormalities observed in long-term culture of mouse cells may result from exposure of cells or medium to fluorescent room lights in the presence of atmospheric oxygen. These genetic abnormalities can be minimized by shielding cells and medium from light, lowering the PO2 of the medium, and including reducing agents such as glutathione and ascorbic acid in the medium formulation.