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)

1. When assayed in fresh homogenates, guinea-pig liver tryptophan pyrrolase exists only as holoenzyme. It does not respond to agents that activate or inhibit the rat liver enzyme in vitro. Only by aging (for 30min at 5 degrees C) does the guinea-pig enzyme develop a requirement for ascorbate. 2. The guinea-pig liver enzyme is activated by the administration of tryptophan but not cortisol, salicylate, ethanol or 5-aminolaevulinate. 3. The tryptophan enhancement of the guinea-pig liver pyrrolase activity is prevented by 0, 34 and 86% by pretreatment with actinomycin D, cycloheximide or allopurinol respectively. 4. The guinea-pig liver tryptophan pyrrolase is more sensitive to tryptophan administration than is the rat enzyme. On the other hand, the concentrations of tryptophan in sera and livers of guinea pigs are 45-52% less than those in rats. 5. It is suggested that tryptophan may regulate the activity of guinea-pig liver tryptophan pyrrolase by mobilizing a latent form of the enzyme whose primary function is the detoxication of its substrate.
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PMID:Guinea-pig liver tryptophan pyrrolase. Absence of detectable apoenzyme activity and of hormonal induction by cortisol and possible regulation by tryptophan. 442 42

Free radicals have been associated with loss of viability of lyophilized bacteria exposed to oxygen. Free radical concentration was proportional to the log of the oxygen pressure in the sample. Sugars, such as lactose or sucrose, preserved viability and inhibited free radical production. Lyophilized tissue, particularly liver and spleen, also reacted with oxygen to produce free radicals, which appear to be associated with ascorbic acid in the tissues. Pure ascorbic acid in air does not produce free radicals, but when mixed with protein before lyophilization it reacts with oxygen in air. When a mixture of sodium ascorbate and phenylalanine or tryptophan is lyophilized, free radicals identical to those observed in tissue are obtained. Propyl gallate and di- or trihydroxybenzoates also react with oxygen when lyophilized with phenylalanine, but the g value of the free radical is significantly less than that obtained with ascorbate. A number of amino acids and similar nitrogenous compounds act as catalysts to form propyl gallate free radicals. As with the bacterial or tissue preparations, various sugars or similar carbohydrates inhibited free radical production by either ascorbate or gallate. In the absence of water the free radicals produced by the action of oxygen on lyophilized samples are stable for years. The rate of free radical production is increased by small amounts of moisture (exposure to moist air), but at humidities over 30% rh the radicals are unstable.
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PMID:Adventitious chemistry at reduced water activities: free radicals and polyhydroxy agents. 631 94

Summation and synergism in the effects of three tumor promoters on urinary bladder carcinogenesis initiated by a 4-week treatment with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male F344 rats were examined. In experiment 1, the sequential administration of sodium saccharin (SS, 5.0%), DL-tryptophan (Tr, 2.0%) and sodium L-ascorbate (SA, 5.0%) in the diet, each for 10 weeks, significantly increased the incidence and the number of bladder tumors over that observed after SS alone or SS followed by Tr. In experiment 2, the simultaneous dietary administration of 2.5% SA, 1.0% butylated hydroxyanisole and 0.01% allopurinol for 32 weeks significantly increased the yield of bladder tumors. Paired combinations of promoters or each of the promoters administered alone were associated with a less pronounced promotive effect than when all three were combined. Thus, it is evident from the results of the present investigation that whatever the mechanisms underlying promotion by the different agents, they are capable of working in an additive fashion, under conditions of summation (consecutive administration) or synergism (simultaneous administration).
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PMID:Summation and synergism in the promotion of urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)-nitrosamine in F344 rats. 651 96

The promoting effects of various chemicals on urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Male Fischer 344 rats were given BBN at 0.01% or 0.05% in their drinking-water for four weeks. One of the following chemicals was then administered in the diet for 32 or 34 weeks: acetazolamide, allopurinol, phenobarbital, phenacetin, ortho-phenylphenol, sodium ortho-phenylphenate, diphenyl, sodium L-ascorbate, butylated hydroxyanisole, butylated hydroxytoluene, sodium saccharin, aspartame, sodium cyclamate, stevioside, DL-tryptophan, quercetin, caffeine, nicotine and hippuric acid. Phenacetin, sodium ortho-phenylphenate, sodium L-ascorbate and butylated hydroxyanisole were significant promoters of urinary bladder neoplasia in rats initiated with BBN. Sodium saccharin, diphenyl, butylated hydroxytoluene, allopurinol, and DL-tryptophan caused moderate or slight promotion of neoplastic changes in the experimental animals. No change in tumour yield was observed after administration of the other chemicals.
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PMID:Drugs, food additives and natural products as promoters in rat urinary bladder carcinogenesis. 653 4

This article examines the effects of oral contraceptives (OCs) on the metabolism of vitamin B6, folacin, vitamin B12, and vitamin C and outlines educational strategies through which nurse-midwives can improve their clients' nutritional health. Evidence of vitamin B6 deficiency has been found among combination OC users in numerous studies. Derangement of tryptophan metabolism occurs within 1 month of initiation of OC use. OCs also may cause a deficiency of pyridoxal phosphate, a coenzyme needed for the tryptophan-nicotinic acid pathway. It is recommended that OC users take 1-1.5 mg/day of supplemental vitamin B6; new OC users should take 5 mg/day until plasma levels of 1.5-2 mg have been achieved. It has also been noted that OCs impair folacin metabolism, as evidenced by folacin deficiency in serum and an increase in urinary formiminoglutamic acid secretion. It is generally ageed that folacin, which plays a critical role in fetal development, can become deficient in late pregnancy and in women who become pregnant shortly after discontinuing longterm OC use. OCs further influence serum B12 concentrations and the possiblity of iron deficiency anemia. Among patients who are well nourished and nonsmokers, OC use does not appear to jeopardize vitamin C levels. An assessment of a patient's nutritional health should begin with a demographic evaluation focused on her age, parity, alcohol and nicotine consumption, and use of medications and vitamins. Next, a dietary evaluation should be made by having the patient record everything she eats during the following week. It should be remembered that adolescents, lactating women, those with repeated pregnancies closely spaced, and women who are chemically dependent have greater nutritional needs than normal. Nutritional counseling is particularly needed by OC users, who may be deficient in 1 or more of the essential vitamins. Nutritional counseling should be an ongoing part of any comprehensive patient-teaching program.
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PMID:Effects of oral contraceptives on vitamins B6, B12, C, and folacin. 656 71

We studied the capacity of various chemicals to promote urinary bladder cancer in male F344 rats after initiation by N-nitroso-n-butyl-(4-hydroxybutyl)amine (BBN). The rats were given initially 0.01% BBN in the drinking-water for 4 wk and then the test compound in the diet for 34 wk. Effects were judged by measuring the formation of preneoplastic lesions papillary or nodular hyperplasia (PN hyperplasia) of the urinary bladder. Administration of 5%, but not 0.5% (w/w) sodium saccharin in the diet significantly increased the incidence and extent of PN hyperplasia. This finding could be related to the induction of cancers in the rat urinary bladder by high levels of saccharin. Sodium ascorbate (5%). DL-tryptophan (5%) and allopurinol (0.02%) also significantly increased the extent of PN hyperplasia in the affected animals, but other test chemicals, such as acetazolamide (0.35%) and quercetin (5%) did not. The results with sodium saccharin and DL-tryptophan were consistent with previous findings and suggest that sodium ascorbate and allopurinol have promoting activities in urinary bladder carcinogenesis in rats. No correlation was found between the extent of crystalluria and promotion of preneoplastic lesions.
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PMID:Promoting effects of various chemicals in rat urinary bladder carcinogenesis initiated by N-nitroso-n-butyl-(4-hydroxybutyl)amine. 668 93

It has been shown that the occurrence of the preneoplastic lesion, papillary or nodular hyperplasia (PN hyperplasia) in rat urinary bladder induced by carcinogens is correlated with that of cancer. Therefore, the promoting effects of chemicals in two-stage bladder carcinogenesis were judged by measuring their ability to induce PN hyperplasia in rats. Male rats were given N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks and then one of 16 test chemicals for 32 to 34 weeks. Saccharin, ascorbate, DL-tryptophan, allopurinol, and diphenyl promoted development of PN hyperplasia. The dose-response of the promoters were examined in both sexes of rats by administration of saccharin at doses of 0.04, 0.2, 1.0 and 5.0% for 32 weeks after BBN treatment. The occurrence of PN hyperplasia was significantly increased in the group given 5% saccharin. Dose-response curves showed enhanced hyperplastic responses in both sexes given 0.2 to 5% saccharin. The organ specificities of promoters were studied in rats initiated with BBN or 2-acetylamino-fluorene (2-AAF) followed by phenobarbital or saccharin for 32 weeks. Phenobarbital greatly enhanced hepatocarcinogenesis. Saccharin significantly enhanced the occurrence of both BBN-induced and 2-AAF-induced PN hyperplasia. However, there was no effect of phenobarbital on the urinary bladder or of saccharin on the liver. The rats showed a strain difference in susceptibility of the urinary bladder to saccharin; ACI rats were most susceptible and Sprague Dawley rats were most resistant to saccharin. The membrane potential of superficial epithelial cells in the urinary bladder of rats treated with saccharin was measured with an intracellular microelectrode and found to be higher than that of controls.
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PMID:Effects of promoters on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in the rat. 687 32

The trichloromethyl peroxy radical Cl3COO reacts with tryptophan, tryptophanyl-tyrosine and with lysozyme to form products whose overall absorption spectrum is different from those observed following the reaction of hydroxyl, bromide, thiocyanate or azide radicals. Two spectral components have been identified: a minor component attributed to the neutral tryptophanyl radical which can react with ascorbate and intramolecularly with tyrosine residues and a major component which does not undergo either of these reactions and is probably a radical adduct.
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PMID:Reactions of the trichloromethylperoxy free radical (Cl3COO) with tryptophan, tryptophanyl-tyrosine and lysozyme. 697 25

Indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase are part of the anti-tumor and antimicrobial activities of mononuclear phagocytes induced by interferon-gamma (IFN gamma). As IDO is a heme-containing enzyme and NO, the product of nitric oxide synthase-initiated arginine degradation, is a regulator of heme enzymes, we investigated whether NO is capable of modulating IDO activity in IFN gamma-primed mononuclear phagocytes. Authentic NO gas or the NO-generating compound, diethylamine dinitric oxide adduct, dose-dependently inhibited IDO activity in cell lysates prepared from IFN gamma-primed human peripheral blood mononuclear cells, as assessed by the ascorbate/methylene blue assay for IDO. In contrast, neither nitrite nor nitrate affected IDO activity. Exposure of intact IFN gamma-primed human peripheral blood mononuclear cells or monocyte-derived macrophages to any of the NO-generating compounds, sodium nitroprusside, glyceryl trinitrate, S-nitroso-N-acetylpenicillamine, or diethylamine dinitric oxide adduct, resulted in inhibition of both the consumption of tryptophan from and formation of its metabolite, kynurenine, in the culture medium. The observed inhibition of IDO activity was not due to toxicity of the NO generators and was abrogated by the co-addition of oxyhemoglobin, an antagonist of NO function. Comparable concentrations of nitrite or nitrate did not inhibit IDO activity in intact cells. In contrast to human cells, addition of IFN gamma to murine macrophages, cultured in complete RPMI 1640 medium, readily induced nitric oxide synthase. Others have reported that such treatment does not induce IDO activity in these cells. However, induction of IDO activity was observed in murine macrophages when the synthesis of reactive nitrogen species was inhibited, by using arginine-free medium and/or the nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine. Together, these results demonstrate that both exogenous and endogenous NO inhibit IDO activity and that oxidative arginine and tryptophan metabolism in IFN gamma-primed mononuclear phagocytes are functionally related. Our study thereby provides an insight into how these cells may regulate some of their antimicrobial and anti-tumor activities.
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PMID:Nitric oxide inhibits indoleamine 2,3-dioxygenase activity in interferon-gamma primed mononuclear phagocytes. 751 70

It is well documented that despite global abnormalities of the immune system in AIDS and other immune deficiency diseases or in immunosuppressed patients, the incidence of only a few kinds of tumor increases, and that the degree of immunosuppression seems not to be a critical factor in the development of even these tumors. The fact that tumors do not develop in the majority of population during their lifetime, despite the ineffectiveness of the known immune system against the majority of tumors, can only be explained by hypothesizing that the living system has an additional defense mechanism against tumors. On the bases of literary data, it can be assumed that the effective agents of this defense mechanism are certain substances of the circulatory system. We proved this hypothesis by being able to select thirteen substances of the circulatory system from 71 compounds tested, using the synergistic tumor cell-killing effect as criteria. The mixture containing the thirteen substances (L-tryptophan, L-tyrosine, L-methionine, L(-)-malate, L-ascorbate, L-arginine, L-phenylalanine, L-histidine, 2-deoxy-D-ribose, d-biotin, pyridoxine, adenine and riboflavin) had a cytotoxic effect against Sp2/0-Ag14 mouse and K562, HEp-2, HeLa and Caco-2 human tumor cell lines in well-controlled conditions, but it was not cytotoxic against Vero normal cell line. The mixture of the above substances increased significantly the survival time of mice (T/C% 148.1) injected i.p. with Sp2/0-Ag14 mouse myeloma cells by killing more than 2 logs (99%) of the cells. Approximately the same 2 logs cell kill was found counting the Sp2/0-Ag14 cells in the ascitic fluid of control and treated animals after finishing treatment. The above mixture slowed down the growth of HeLa solid tumor significantly (T/C%, the least value 35.7). The weight loss of control and treated group during treatment did not differ significantly.
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PMID:Inhibition of the growth of a murine and various human tumor cell lines in culture and in mice by mixture of certain substances of the circulatory system. 766 76


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