Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00568 (ascorbate)
 23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible influence of dietary antioxidants, especially vitamin C, on the increasing prevalence of asthma is explored. Vitamin C intake in the general population appears to correlate with asthma, suggesting that a diet low in vitamin C is a risk factor for asthma. Epidemiological studies show associations among oxidant exposure, respiratory infections, and asthma in children of smokers. Symptoms of ongoing asthma in adults appear to be increased by exposure to environmental oxidants and decreased by vitamin C supplementation. There is evidence that oxidants produced endogenously by overactive inflammatory cells contribute to ongoing asthma. Vitamin C is the major antioxidant substance present in the airway surface liquid of the lung, where it could be important in protecting against both endogenous and exogenous oxidants. Nitrogen oxides are exemplary of oxidants that could arise from both endogenous and environmental sources, which are protected against by vitamin C, and that may be important in causation and propagation of asthma.
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PMID:Asthma, inhaled oxidants, and dietary antioxidants. 787 29

Nitric oxide (nitrogen monoxide, NO) at low concentrations can potently deenergize isolated liver and brain mitochondria at oxygen concentrations that prevail in cells and tissues. Deenergization is observed when mitochondria utilize respiratory substrates such as pyruvate plus malate, succinate, or ascorbate plus tetramethylphenylenediamine, but not when mitochondria are energized with ATP. The extent and duration of deenergization is determined by the concentration of NO and oxygen, and the kind of respiratory substrate. The NO-induced changes of the mitochondrial energy state are transient and are paralleled by release and reuptake of mitochondrial calcium. These findings reveal a direct action of NO on the mitochondrial respiratory chain and suggest that NO exerts some of its physiological and pathological effects by deenergizing mitochondria.
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PMID:Nitric oxide potently and reversibly deenergizes mitochondria at low oxygen tension. 794 56

The marketable and nutritional quality of crisphead lettuce as affected by nitrogen supply, cultivar, and plant age at harvest was investigated in six plantings during 1989 and 1990. The optimum yield of marketable heads was obtained at a total nitrogen supply of 150 kg N per ha although only small differences were observed to the yield at 100 and 200 kg total N per ha. The total nitrogen supply included the amount of mineral nitrogen within the rhizosphere. The incidence of dry tipburn in older leaves was clearly decreased by an increased nitrogen supply, especially at late planting. The content of nitrate was increased and the content of dry matter and vitamin C decreased with increased nitrogen supply. The vitamin C content was higher for the cultivar 'Marius' than for 'Saladin'. As plants got older, the nutritional quality of crisphead lettuce decreased because the content of nutrients, especially vitamin C, decreased with increased plant age at harvest.
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PMID:Influence of growth conditions on the value of crisphead lettuce. 1. Marketable and nutritional quality as affected by nitrogen supply, cultivar and plant age. 797 81

Atrophic gastritis is precancerous condition of the intestinal type of gastric carcinoma. This process supposes a genotoxic effect of N-nitroso-compounds which are formed in the stomach by nitrosation of nitrites and organic nitrogen compounds. The authors examined 41 patients with chronic superficial and atrophic gastritis. They examined the pH and concentration of nitrates and nitrites in gastric juice taken in the morning before meal. They discovered that in severe atrophic gastritis the amount of nitrates is significantly increased and the amount of nitrites is decreased, all in comparison with superficial gastritis. An exponential relation of the concentration of nitrites towards the pH of gastric juice was found to be NO2- = epH-6.5, CC = 0.935. A significant elevation of nitrite concentration was observed in cases of pH being higher than 5.5. Nitrate concentration altered in dependence of the value of gastric pH. Oral administration of 300 mg of vitamin C or 250 mg of vitamin E did not significantly affect the amount of gastric nitrites. The work discusses the mutual relation of nitrites, ascorbic acid and alpha-tocopherol towards the formation of N-nitroso-compounds in the stomach inflicted by atrophic gastritis. (Tab. 3, Fig. 2, Ref. 25.)
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PMID:[Nitrates and nitrites in gastric juice in chronic gastritis]. 800 72

Adriamycin-Fe(3+)-induced lipid peroxidation was enhanced by ascorbate at low concentrations. High concentrations of ascorbate also enhanced the peroxidation reaction, but only at an early stage. The initial rate of peroxidation depended upon the ratio of adriamycin-Fe2+/adriamycin-Fe3+ and the maximum rate was observed at the ratio of 1:1. These results suggest that the adriamycin-Fe(3+)-induced lipid peroxidation may be initiated by an adriamycin-Fe(2+)-oxygen-adriamycin-Fe3+ complex. Ascorbate also promoted bathophenanthroline-Fe2+ formation from adriamycin-Fe3+ in a dose-dependent manner. It seems likely that ascorbate influences the peroxidation reaction via the reduction of adriamycin-Fe3+. During the interaction of adriamycin-Fe3+ with ascorbate, deoxyribose was not degraded, suggesting that hydroxyl radical formation did not occur. In contrast, plasmid PM2 DNA was readily damaged during the interaction of adriamycin-Fe3+ with ascorbate. Catalase, mannitol and dimethylsulfoxide prevented DNA damage. No DNA damage occurred when the reaction was run under nitrogen gas, indicating that oxygen is involved.
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PMID:Effect of ascorbate on adriamycin-Fe(3+)-induced lipid peroxidation and DNA damage. 819 Jul 8

To determine correlates of the geographic variation in colon cancer mortality within China, dietary variables, biochemical markers, and other factors from an ecological survey in 49 Chinese rural counties were examined. High consumption of animal foods, salt-preserved vegetables, and beer was associated with increased mortality of colon cancer, whereas the rates were significantly inversely related with intake of green vegetables. Serum levels of total cholesterol, urea nitrogen, and lipid peroxide were positively correlated with colon cancer mortality, after adjustment for each other and for other blood nutrients. No appreciable associations, however, were found between colon cancer and serum levels of beta-carotene, alpha-tocopherol, vitamin C, and selenium. In addition, prevalence of schistosomiasis was significantly correlated with increased colon cancer mortality. This ecological study indicates that observations from earlier analytic investigations in Western societies may apply to a Chinese rural population and suggests that schistosomiasis and dietary factors may contribute to the remarkable geographic variation of colon cancer in China.
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PMID:Correlations of colon cancer mortality with dietary factors, serum markers, and schistosomiasis in China. 841 26

The stoichiometric reductive debromination of BrCCl3 to a trichloromethyl radical by myoglobin caused the prosthetic heme to become covalently cross-linked to the protein moiety and transformed myoglobin from an oxygen storage protein to an oxidase. This was shown in experiments in which oxygen consumption was measured during redox cycling of the altered myoglobin in the presence of ascorbate or an enzymatic reducing system containing diaphorase and NADH. Redox cycling eventually led to loss of the protein-bound heme adduct and oxidase activity of myoglobin. We have used molecular modeling and the known structure of the protein-bound heme adduct to identify probable mechanisms for transformation of myoglobin to an oxidase. Based on these modeling studies, the most likely structure of the experimentally observed adduct involves ligation to the heme iron of the epsilon-nitrogen atom of histidine 97 and/or that of histidine 64. The model structures revealed access of solvent to the heme active site, which could facilitate oxygen reduction. The transformation of myoglobins and perhaps other hemoproteins to oxidases may have toxicological importance in causing the tissue damage resulting from exposure to various xenobiotics and endogenous chemicals as well as explaining how hemoproteins are inactivated during catalysis.
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PMID:Metabolism-based transformation of myoglobin to an oxidase by BrCCl3 and molecular modeling of the oxidase form. 842 69

Isoquinoline derivatives exert 1-methyl-4-phenylpyridinium (MPP+)-like activity as inhibitors of complex I and alpha-ketoglutarate dehydrogenase activity in rat brain mitochondrial fragments. We now examine the ability of 19 isoquinoline derivatives and MPP+ to accumulate and inhibit respiration in intact rat liver mitochondria, assessed using polarographic techniques. None of the compounds examined inhibited respiration supported by either succinate + rotenone or tetramethylparaphenylenediamine (TMPD) + ascorbate. However, with glutamate + malate as substrates, 15 isoquinoline derivatives and MPP+ inhibited state 3 and, to a lesser extent, state 4 respiration in a time-dependent manner. None of the isoquinoline derivatives were more potent than MPP+. 6,7-Dimethoxy-1-styryl-3,4-dihydroisoquinoline uncoupled mitochondrial respiration. Qualitative structure-activity relationship studies revealed that isoquinolinium cations were more active than isoquinolines in inhibiting mitochondrial respiration; these, in turn, were more active than dihydroisoquinolines and 1,2,3,4-tetrahydroisoquinolines. Three-dimensional quantitative structure-activity relationship studies using Comparative Molecular Field Analysis showed that the inhibitory potency of isoquinoline derivatives was determined by steric, rather than electrostatic, properties of the compounds. A hypothetical binding site was identified that may be related to a rate-limiting transport process, rather than to enzyme inhibition. In conclusion, isoquinoline derivatives are less potent in inhibiting respiration in intact mitochondria than impairing complex I activity in mitochondrial fragments. This suggests that isoquinoline derivatives are not accumulated by mitochondria as avidly as MPP+. The activity of charged and neutral isoquinoline derivatives implicates both active and passive processes by which these compounds enter mitochondria, although the quaternary nitrogen moiety of the isoquinolinium cations favours mitochondrial accumulation and inhibition of respiration. These findings suggest that isoquinoline derivatives may exert mitochondrial toxicity in vivo similar to that of MPTP/MPP+.
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PMID:Effects of isoquinoline derivatives structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mitochondrial respiration. 863 91

Production of reactive species has been associated with tissue injury in diverse human disorders and experimental models of disease. Peroxynitrite is a strong oxidant with multiple pathways of reactivity. One protein modification reaction that may be specific to peroxynitrite is the nitration of the ortho position of tyrosine residues and nitrotyrosine has been used as a marker for peroxynitrite-mediated oxidative stress. Nitrotyrosine was formed when peroxynitrite was reacted at physiological pH with fatty acid-free bovine serum albumin or with human plasma proteins. Nitrotyrosine was not formed when proteins were incubated with nitric oxide, nitrogen dioxide, or nitric oxide plus hydrogen peroxide in the presence of ferrous iron or ferrihorseradish peroxidase. Low-molecular-weight molecules such as uric acid, ascorbate, and sulfhydryls inhibited protein tyrosine nitration in the absence of bicarbonate. Addition of bicarbonate catalytically enhanced the yield of nitration and overcame the inhibition of these antioxidants. Bicarbonate/CO2 enhanced the yield of protein nitrotyrosine in a concentration-dependent manner. Catalysis of nitration is achieved by the interaction of CO2 with the peroxynitrite anion. A mechanism is proposed involving an ONOO(O)CO- intermediate, which readily nitrates tyrosine residues in a non-radical-dependent manner. Thus, peroxynitrite nitrates tyrosine residues by a mechanism that is catalyzed by CO2 under normal physiological conditions.
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PMID:Carbon dioxide enhancement of peroxynitrite-mediated protein tyrosine nitration. 880 52

Excessive use of nitrogen fertilizers is known to increase the NO3 and reduce the vitamin C contents in fruits and vegetables. We investigated the concentration of these compounds in spinach leaves when plants were transferred to nitrogen-free media prior to their harvest. It was noted that a pre-harvest transfer of spinach to N-free media reduces the NO3 and increases the vitamin C content of the leaves by a substantial amount in a 2-3 day period. It is suggested that this technique may be suited to produce spinach or other leafy vegetables with low NO3 and high vitamin C contents under commercial hydroponic conditions.
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PMID:Decreasing the NO3 and increasing the vitamin C contents in spinach by a nitrogen deprivation method. 881 29


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