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)

In this population-based case-control study conducted in California between June 1989 and May 1991, the authors investigated the association between maternal periconceptional exposure to nitrate from drinking water and diet and risk for neural tube defects. The mothers of 538 cases and 539 nonmalformed controls were interviewed regarding residential history, consumption of tap water at home, and dietary intake during the periconceptional period. Dietary nitrate exposure was not associated with increased risk for neural tube defects. Exposure to nitrate in drinking water at concentrations above the 45 mg/liter maximum contaminant level was associated with increased risk for anencephaly (odds ratio (OR) = 4.0, 95% confidence interval (CI): 1.0, 15.4), but not for spina bifida. Increased risks for anencephaly were observed at nitrate levels below the maximum contaminant level among groundwater drinkers only (OR = 2.1, 95% CI: 1.1,4.1 for 5-15 mg/liter; OR = 2.3, 95% CI: 1.1, 4.5 for 16-35 mg/liter; and OR = 6.9, 95% CI: 1.9, 24.9 for 36-67 mg/liter compared with <5 mg/liter). Adjustment for identified risk factors for anencephaly did not substantially alter these associations, nor did control for maternal dietary nitrate, total vitamin C intake, and quantity of tap water consumed. The lack of an observed elevation in risk for anencephaly in association with exposure to mixed water containing nitrate at levels comparable with the concentration in groundwater may indicate that something other than nitrate accounts for these findings.
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PMID:Maternal exposure to nitrate from drinking water and diet and risk for neural tube defects. 1120 49

Nitrate contamination of drinking water may increase cancer risk, because nitrate is endogenously reduced to nitrite and subsequent nitrosation reactions give rise to N-nitroso compounds; these compounds are highly carcinogenic and can act systemically. We analyzed cancer incidence in a cohort of 21,977 Iowa women who were 55-69 years of age at baseline in 1986 and had used the same water supply more than 10 years (87% > 20 years); 16,541 of these women were on a municipal supply, and the remainder used a private well. We assessed nitrate exposure from 1955 through 1988 using public databases for municipal water supplies in Iowa (quartile cutpoints: 0.36, 1.01, and 2.46 mg per liter nitrate-nitrogen). As no individual water consumption data were available, we assigned each woman an average level of exposure calculated on a community basis; no nitrate data were available for women using private wells. Cancer incidence (N = 3,150 cases) from 1986 through 1998 was determined by linkage to the Iowa Cancer Registry. For all cancers, there was no association with increasing nitrate in drinking water, nor were there clear and consistent associations for non-Hodgkin lymphoma; leukemia; melanoma; or cancers of the colon, breast, lung, pancreas, or kidney. There were positive associations for bladder cancer [relative risks (RRs) across nitrate quartiles = 1, 1.69, 1.10, and 2.83] and ovarian cancer (RR = 1, 1.52, 1.81, and 1.84), and inverse associations for uterine cancer (RR = 1, 0.86, 0.86, and 0.55) and rectal cancer (RR = 1, 0.72, 0.95, and 0.47) after adjustment for a variety of cancer risk/protective factors, agents that affect nitrosation (smoking, vitamin C, and vitamin E intake), dietary nitrate, and water source. Similar results were obtained when analyses were restricted to nitrate level in drinking water from 1955 through 1964. The positive association for bladder cancer is consistent with some previous data; the associations for ovarian, uterine, and rectal cancer were unexpected.
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PMID:Municipal drinking water nitrate level and cancer risk in older women: the Iowa Women's Health Study. 1133 13

Most nitrite entering the healthy acid-secreting stomach is derived from dietary nitrate. The latter is absorbed from the small intestine, 25% then being secreted by the salivary glands into the mouth. Buccal organisms subsequently convert 20% of this nitrate to nitrite. When this nitrite is swallowed, the ascorbic acid in the acidic gastric juice reduces it to nitric oxide, which is absorbed by the mucosa. In the process, the ascorbic acid is oxidized to dehydroascorbic acid. When the intragastric pH is elevated by powerful anti-secretory agents, this gastric chemistry is profoundly modified. At a neutral pH, the swallowed nitrite does not react with ascorbic acid but accumulates in the stomach. The level of nitrite in the gastric juice during treatment with anti-secretory medication is particularly high after a nitrate-containing meal. Powerful anti-secretory medication also lowers the intragastric concentration of ascorbic acid and total vitamin C, probably because of the relative instability of the vitamin at a higher pH. These changes in the intragastric concentrations of nitrite and ascorbic acid are most marked in Helicobacter pylori -infected subjects on proton pump inhibitor therapy. It is recognized that an elevated nitrite-to-ascorbic acid ratio predisposes to the formation of potentially carcinogenic N -nitroso compounds. It is, however, unclear at present whether such compounds are formed within the human stomach.
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PMID:Alterations in intragastric nitrite and vitamin C levels during acid inhibitory therapy. 1140 44

Experiments have been carried out with field-grown pear trees to investigate the effect of iron chlorosis on the composition of the leaf apoplast. Iron deficiency was associated with an increase in the leaf apoplastic pH from the control values of 5.5-5.9 to 6.5-6.6, as judged from direct pH measurements in apoplastic fluid obtained by centrifugation and fluorescence of leaves incubated with 5-CF. The major organic acids found in leaf apoplastic fluid of iron-deficient and iron-sufficient pear leaves were malate, citrate and ascorbate. The total concentration of organic acids was 2.9 mM in the controls and increased to 5.5 mM in Fe-deficient leaves. The total apoplastic concentration of inorganic cations (Ca, K and Mg) increased with Fe deficiency from 15 to 20 mM. The total apoplastic concentration of inorganic anions (Cl-, NO3-, SO4(2-) and HPO4(2-)) did not change with Fe deficiency. Iron concentrations decreased from 4 to 1.6 microM with Fe deficiency. The major Fe species predicted to exist in the apoplast was [FeCitOH](-1) in both Fe-sufficient and deficient leaves. Organic acids in whole leaf homogenates increased from 20 to 40 nmol x m(-2) with Fe deficiency. The accumulation of organic anions in the Fe-deficient leaves does not appear to be associated to an increased C fixation in leaves, but rather it seems to be a consequence of C transport via xylem.
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PMID:Iron deficiency-associated changes in the composition of the leaf apoplastic fluid from field-grown pear (Pyrus communis L.) trees. 1145 9

Antioxidant treatment has previously been shown to be neuroprotective in experimental bacterial meningitis. To obtain quantitative evidence for oxidative stress in this disease, we measured the major brain antioxidants ascorbate and reduced glutathione, and the lipid peroxidation endproduct malondialdehyde in the cortex of infant rats infected with Streptococcus pneumoniae. Cortical levels of the two antioxidants were markedly decreased 22 h after infection, when animals were severely ill. Total pyridine nucleotide levels in the cortex were unaltered, suggesting that the loss of the two antioxidants was not due to cell necrosis. Bacterial meningitis was accompanied by a moderate, significant increase in cortical malondialdehyde. While treatment with either of the antioxidants alpha-phenyl-tert-butyl nitrone or N-acetylcysteine significantly inhibited this increase, only the former attenuated the loss of endogenous antioxidants. Cerebrospinal fluid bacterial titer, nitrite and nitrate levels, and myeloperoxidase activity at 18 h after infection were unaffected by antioxidant treatment, suggesting that they acted by mechanisms other than modulation of inflammation. The results demonstrate that bacterial meningitis is accompanied by oxidative stress in the brain parenchyma. Furthermore, increased cortical lipid peroxidation does not appear to be the result of parenchymal oxidative stress, because it was prevented by NAC, which had no effect on the loss of brain antioxidants.
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PMID:Oxidative stress in brain during experimental bacterial meningitis: differential effects of alpha-phenyl-tert-butyl nitrone and N-acetylcysteine treatment. 1155 13

Consumer concern regarding possible adverse health effects of foods produced using intensive farming methods has led to considerable interest in the health benefits of organically-produced crops and animal products. There appears to be widespread perception amongst consumers that such methods result in foods of higher nutritional quality. The present review concludes that evidence that can support or refute such perception is not available in the scientific literature. A limited number of studies have compared the nutrient compositions of organically- and conventionally-produced crops, with a very small number of studies that have compared animal products (meat, milk and dairy products) produced under the two agricultural systems. Very few compositional differences have been reported, although there are reasonably consistent findings for higher nitrate and lower vitamin C contents of conventionally-produced vegetables, particularly leafy vegetables. Data concerning possible impacts on animal and human health of diets comprising organic or conventional produce are extremely sparse. Data from controlled studies in animal models, particularly within single species, are limited or poorly designed, and findings from these studies provide conflicting conclusions. There are no reports in the literature of controlled intervention studies in human subjects. Comparison of health outcomes in populations that habitually consume organically- or conventionally-produced foods are flawed by the large number of confounding factors that might contribute to any differences reported. If consumer perceptions regarding potential health benefits of organic foods are to be supported, more research of better quality is needed than that which is currently available.
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PMID:Nutritional quality of organic food: shades of grey or shades of green? 1200 90

Increased inactivation of nitric oxide (NO) by superoxide has been implicated in nitrate tolerance. Here, we set out to compare the inhibitory effect of superoxide on endothelium-dependent, acetylcholine (ACh)-mediated vascular relaxation with that on the endothelium-independent effects of glyceryl trinitrate (GTN) and another NO donor drug, S-nitrosoglutathione (GSNO). Rings of thoracic aorta from adult male Wistar rats (350-450 g) were precontracted with phenylephrine (approximately EC(90)) prior to cumulative additions (10 nM/L-10 microM/L) of GTN, GSNO, or ACh. Rings were then treated with the superoxide generator pyrogallol (300 micromol/L) alone or following pretreatment with the Cu/Zn superoxide dismutase inhibitor diethyldithiocarbamate (DETCA; 100 micromol/L), and cumulative additions of the vasodilators were repeated. All experiments were conducted in the presence of catalase (3000 U/ml) to prevent accumulation of hydrogen peroxide. Relaxation to ACh was abolished by pyrogallol-derived superoxide. Relaxation to GSNO was significantly inhibited by superoxide (P < 0.05, n = 8) and was more pronounced at lower GSNO concentrations. However, GTN was relatively resistant to inhibition by superoxide with modest inhibition only occurring in rings pretreated with DETCA prior to pyrogallol (P < 0.05; n = 8). In contrast to GSNO, the inhibitory effect was more pronounced with high concentrations of GTN, suggesting that the mechanism underlying superoxide-mediated inhibition is different for the two NO donor drugs. Further experiments showed that vascular responses to ACh were not inhibited (P > 0.05, n = 6) in aortic rings made tolerant to GTN (10 micromol/L, 2-h incubation) and that treatment of vessels with the antioxidant vitamin C (1 mmol/L) successfully prevented the development of tolerance. Taken together, these results suggest that superoxide is not a major factor in tolerance in vitro and imply that the protective actions of vitamin C are unrelated to its antioxidant activity in this setting.
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PMID:The effect of oxidative stress on endothelium-dependent and nitric oxide donor-induced relaxation: implications for nitrate tolerance. 1200 44

Cadmium is a potent carcinogen in rodents and has recently been accepted by the International Agency for Research on Cancer as a category 1 (human) carcinogen, but the molecular mechanism of its action remains largely unclear. It has however been suggested that cadmium-induced carcinogenesis may involve either direct or indirect interaction of Cd(2+) with DNA. Cd(2+) is believed to bind covalently with N7 centres of adenine and guanine. At low concentrations (< or =50 mM), Cd(2+) is found to react with plasmid DNA to produce a mixture of Form I and Form II bands whereas at higher concentrations (> or =100 mM), Cd(2+) causes extensive damage to DNA at a pH 5.8 solution of cadmium nitrate. Within the range 0-100 mM (when pH is adjusted to 7.4 by adding NaOH) an increase in concentration of Cd(2+) is found to cause a decrease in the gel mobility rate of plasmid and an increase in the intensity of the Form II band. When plasmid DNA is digested with BamH1, only the Form III band is observed both in the presence and absence of Cd(2+). However, the mobility of the band is found to decrease with the increase in the concentration of Cd(2+). When the enzyme Ssp1 which cuts plasmid DNA at the AT sites is used instead of BamH1, two bands are observed in the presence of cadmium as against one band in the absence of cadmium. These results suggest that Cd(2+) binds covalently with DNA (possibly at G, A and T centres) and can form intrastrand bifunctional AT adducts but not the GG adducts. It may also be that neither GG nor AT adducts are formed and yet Ssp1 digestion is prevented because of a structural modification introduced in adenine by its interaction with Cd(2+). In the presence of antioxidants such as cysteine, glutathione and ascorbate (especially cysteine and ascorbate), DNA damage is found to be greater than expected for the combined effects of the antioxidant and Cd(2+). The increased DNA damage is believed to be due to the formation of reactive oxygen species (ROS).
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PMID:Studies on the interaction between Cd(2+) ions and DNA. 1203

Lipopolysaccharide endotoxin and interferon-gamma induced inducible nitric oxide synthase (iNOS) protein expression and nitrite/nitrate formation in microvascular endothelial cell cultures (ECs) derived from rat skeletal muscle. Pretreatment of ECs with ascorbate accumulated a large amount of ascorbate inside the cells and consequently decreased both intracellular oxidant level and iNOS induction. These effects of ascorbate were abolished in the presence of exogenous superoxide generated by xanthine oxidase/xanthine plus catalase but were not altered when N-nitro-L-arginine methyl ester was applied to inhibit nitric oxide synthesis. Ascorbate also attenuated the activation of transcription factor IRF-1 but not NF kappa B. These results indicate that ascorbate inhibits iNOS expression in ECs by an antioxidant mechanism independent of both NF kappa B activation and the reported negative feedback effect of nitric oxide.
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PMID:Ascorbate inhibits iNOS expression in endotoxin- and IFN gamma-stimulated rat skeletal muscle endothelial cells. 1204 83

Syntrophic cocultures of Geobacter sulfurreducens and Wolinella succinogenes oxidize acetate with nitrate as terminal electron acceptor. It has been postulated earlier that electrons are transferred in these cocultures not via hydrogen, but via a different carrier, e.g., a small c-type cytochrome that is detected in the supernatant of growing cultures. In the present study, L -cysteine, which was provided as a reducing agent, was found to mediate the electron transfer between the two partners. Low concentrations of L -cysteine or L -cystine (10-100 microM) supported syntrophic growth, and no acetate oxidation was observed in the absence of cysteine or cystine. Cell suspensions of G. sulfurreducens or coculture cell suspensions reduced cystine to cysteine, and suspensions of W. succinogenes or coculture suspensions oxidized cysteine with nitrate, as measured by the formation or depletion of free thiol groups. Added cysteine was rapidly oxidized by the coculture during growth, but the formed cystine was not entirely rereduced even under acceptor-limited conditions. The redox potential prevailing in acetate-oxidizing cocultures was -160 to -230 mV. Sulfide at low concentrations supported syntrophic growth as well and could replace cysteine. Neither growth nor acetate degradation was found with D-cysteine, homocysteine, cysteamine, 3-mercaptopropionate, dithiothreithol, thioglycolate, glutathione, coenzyme M, dimethylsulfoxide, trimethylamine- N-oxide, anthraquinone-2,6-disulfonate, or ascorbate.
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PMID:Cysteine-mediated electron transfer in syntrophic acetate oxidation by cocultures of Geobacter sulfurreducens and Wolinella succinogenes. 1207 Jul 69


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