Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of enzymic systems of biosynthesis and decay of nicotinamide coenzymes under the effect of extremal and pathogenic factors have shown that the activation of enzymes of the nucleosidase cleavage of coenzymes is the most essential link in the mechanism of concentration disturbance of metabolically active vitamin PP forms under cooling and development of inflammatory processes in the myocardium and liver. Inhibition of the enzymic activity in the biosynthesis of coenzymes under allergic myocarditis and hepatitis may play a definite role in the mechanism of disturbance of the coenzymic function of vitamin PP.
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PMID:[Nicotinamide coenzyme levels and activity of enzymes of their biosynthesis and degradation in animal tissues after exposure to extreme conditions and pathogenic factors]. 300 86

After application of D-galactosamine a hepatitis develops in the rat liver. This can be prevented by different agents, including tryptophan. Yet it has not been possible to give definitive conclusions about the mechanism of galactosamine hepatitis. In this paper we report about the influence of galactosamine on the NAD metabolism. D-galactosamine inhibits the NAD synthesis initiated by nicotinamide in normal and adrenalectomized animals. The NAD synthesis from tryptophan is prevented in normal animals, in adrenalectomized ones however there is an increase of NAD in the presence of D-galactosamine reduces the activity of the ADPR transferase. Inhibitors of the ADPR transferase prevent the galactosamine hepatitis. From the results presented we conclude that the ADPR transferase plays an important role in the development of the galactosamine hepatitis.
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PMID:Influence of D-galactosamine upon the NAD-metabolism in rat liver. 631 40

After administration of D-galactosamine-HCl alterations in liver cells - histologically resembling hepatitis - occur. During this process several biochemical changes are demonstrable. The formation of these alterations may be prevented by combined administration of nicotinamide + L-methionine or DL-tryptophan + L-methionine. This had been confirmed by histology as well as by determination of GOT and GPT activity in the serum.
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PMID:The influence of nicotinamide, tryptophan, and methionine upon galactosamine-induced effects in the liver. 645 26

Content of cytochromes P-450 and b5 and the rate of oxidative dealkylation in liver microsomes as well as the antipyrine pharmacokinetics were normalized in rats with acute CCl4-induced hepatitis after treatment with cordiamine (diethyl nicotinamide) at a dose of 40 mg, subcutaneously, 2 times daily within 4 days. Cordiamine (30 drops 3 times daily within 8 days) contributed to normalization of the hydroxylating reaction in liver tissue of patients with viral hepatitis A, estimated by the "antipyrine" test. The drug exhibited stabilizing effect on hydrophobic interactions in microsomal membranes; diethyl nicotinamide possessed antiradical and vitamin properties.
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PMID:[Correction of disorders in the monooxygenase system function with diethylnicotinamide (cordiamine) in tetrachloromethane- induced and viral hepatitis]. 827 44

The in vitro metabolic activation of flutamide, a nitroaromatic antiandrogen which produces hepatitis in a few recipients, was first studied with male rat liver microsomes. There was no electron spin resonance evidence for the reduction of flutamide by reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase into a nitro anion free radical. In contrast, flutamide was oxidatively transformed by cytochrome P-450 into reactive metabolite(s) that covalently bound to microsomal proteins. Covalent binding required oxygen and NADPH, and was decreased by the nucleophile glutathione and by the cytochrome P-450 inhibitors SKF 525-A, piperonyl butoxide and troleandomycin (an inhibitor of the cytochrome P-450 3A subfamily). Covalent binding was increased markedly by pretreatment with dexamethasone (an inducer of the cytochrome P-450 3A subfamily) and moderately by pretreatment with beta-naphthoflavone (an inducer of the 1A family). Covalent binding was immunoinhibited markedly by anticytochrome P-450 3A immunoglobulin G and moderately by anticytochrome P-450 1A immunoglobulin G. Covalent binding was much lower with liver microsomes from female rats (not expressing P-450 3A2). Covalent binding of flutamide also occurred with human liver microsomes (where it was inhibited by troleandomycin), and with yeast microsomes expressing human liver cytochromes P-450 1A1, 1A2 or 3A4. We concluded that flutamide was oxidatively transformed into chemically reactive metabolite(s) by rat and human cytochromes P-450, including forms belonging to the 3A and 1A subfamilies.
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PMID:Metabolic activation of the nitroaromatic antiandrogen flutamide by rat and human cytochromes P-450, including forms belonging to the 3A and 1A subfamilies. 838 41

Halothane hepatitis occurs because susceptible patients mount immune responses to trifluoroacetylated protein antigens, formed following cytochrome P450-mediated bioactivation of halothane to trifluoroacetyl chloride. In the present study, an in vitro approach has been used to investigate the cytochrome P450 isozyme(s) which catalyze neoantigen formation and to explore the protective role of non-protein thiols (cysteine and reduced glutathione). Significant levels of trifluoroacetyl protein antigens were generated when human liver microsomes, and also microsomes from livers of rats pre-treated with isoniazid, phenobarbital or beta-naphtoflavone, were incubated with halothane plus a nicotinamide adenine dinucleotidephosphate (NADPH) generating system. Immunoblotting studies revealed that the major trifluoroacetyl antigens expressed in vitro exhibited molecular masses of 50-55 kDa and included 60 and 80 kDa neoantigens recognized by antibodies from patients with halothane hepatitis. Much lower concentrations of halothane were required to produce maximal antigen generation in isoniazid-induced rat microsomes, as compared with phenobarbital or isosafrole-induced microsomes (0.5 vs 12.5 microl/ml). In isoniazid-induced microsomes, antigen generation was inhibited > 90% by the nucleophiles cysteine and glutathione and by the CYP2E1-selective inhibitors diallylsulfide and p-nitrophenol, but was unaffected by inhibitors of other P450 isozymes (furafylline, sulfaphenazole or triacetyloleandomycin). Neoantigen formation in six human liver microsomal preparations was inhibited in the presence of diallylsulfide, but not by furafylline, sulfaphenazole or triacetyloleandomycin, and exhibited marked variability which correlated with CYP2E1 levels. These results suggest that the balance between metabolic bioactivation by CYP2E1 and detoxication of reactive metabolites by cellular nucleophiles could be an important metabolic risk factor in halothane hepatitis.
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PMID:Interindividual variability in P450-dependent generation of neoantigens in halothane hepatitis. 987 5

Oxidative stress has emerged as a constant feature of chronic renal failure (CRF). The presence of oxidative stress in CRF is evidenced by an overabundance of lipid, carbohydrate, and protein oxidation products in the plasma and tissues of uremic patients and animals. We recently have shown that oxidative stress in CRF animals is associated with and, in part, owing to up-regulation of superoxide-producing enzyme, nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase, and down-regulation of superoxide dismutase (SOD). The functional significance of these findings was confirmed by favorable response to administration of the cell-permeable SOD-mimetic agent, tempol, in CRF rats. Oxidative stress in CRF plays an important role in the pathogenesis of the associated hypertension (oxidation of NO and arachidonic acid and vascular remodeling), cardiovascular disease (oxidation of lipoproteins, atherogenesis), neurologic disorders (nitration of brain proteins, oxidation of myelin), anemia (reduction of erythrocyte lifespan), inflammation (nuclear factor kappa B activation), fibrosis, apoptosis, and accelerated aging. The CRF-induced oxidative stress is aggravated by diabetes, uncontrolled hypertension, and autoimmune diseases, which independently increase production of reactive oxygen intermediates, and frequently are associated with CRF. In addition, dialysis treatment (blood interaction with dialyzer membrane and dialysate impurities), acute and chronic infections (blood access infection, hepatitis, and so forth), and excessive parenteral iron administration intensify CRF-associated oxidative stress and its adverse consequences in patients with end-stage renal disease. The problem is compounded by limited intake of fresh fruits and vegetables (K(+) restriction), which contain numerous natural phytochemicals and antioxidant vitamins.
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PMID:Oxidative stress in uremia: nature, mechanisms, and potential consequences. 1549 Apr 13

Adenine nucleotides induce danger signals in T cells via purinergic receptors, raising the question whether they exert similar effects on innate immunity. Here we show that micromolar concentrations of nicotinamide adenine dinucleotide (NAD) induce a rapid increase of annexin V staining in NKT cells in vitro, a response that requires expression of P2X(7)Rs. Consistent with this result, treatment of mice with NAD causes a temporary decrease of NKT cells in the liver and protects from Con A- and alpha-galactosylceramide-induced hepatitis, both of which require functional NKT cells. Resistance to liver injury is associated with decreased cytokine production by NKT cells in NAD-treated mice. In contrast, when NAD is injected into Con A- or alpha-galactosylceramide-primed mice, liver injury is exacerbated and cytokine production by NKT cells is increased. This effect is caused by P2X(7)R-mediated stimulation of activated NKT cells. In agreement, mice lacking P2X(7)Rs on lymphocytes suffer reduced liver injury, and animals lacking ADP-ribosyltransferase, the enzyme that uses NAD to attach ADP-ribosyl groups to cell surfaces, are also resistant to Con A-induced hepatitis. These results prompt the conclusion that engagement of P2X(7)Rs on NKT cells inhibits naive, while stimulating activated cells, resulting in suppression or stimulation of autoimmune hepatitis.
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PMID:P2X7 receptors regulate NKT cells in autoimmune hepatitis. 1645 71

[1-(13)C]pyruvate is a readily polarizable substrate that has been the subject of numerous magnetic resonance spectroscopy (MRS) studies of in vivo metabolism. In this work (13)C-MRS of hyperpolarized [1-(13)C]pyruvate was used to interrogate a metabolic pathway involved in neither aerobic nor anaerobic metabolism. In particular, ethanol consumption leads to altered liver metabolism, which when excessive is associated with adverse medical conditions including fatty liver disease, hepatitis, cirrhosis, and cancer. Here we present a method for noninvasively monitoring this important process in vivo. Following the bolus injection of hyperpolarized [1-(13)C]pyruvate, we demonstrate a significantly increased rat liver lactate production rate with the coadministration of ethanol (P = 0.0016 unpaired t-test). The affect is attributable to increased liver nicotinamide adenine dinucleotide (NADH) associated with ethanol metabolism in combination with NADH's role as a coenzyme in pyruvate-to-lactate conversion. Beyond studies of liver metabolism, this novel in vivo assay of changes in NADH levels makes hyperpolarized [1-(13)C]pyruvate a potentially viable substrate for studying the multiple in vivo metabolic pathways that use NADH (or NAD(+)) as a coenzyme, thus broadening the range of applications that have been discussed in the literature to date.
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PMID:In vivo measurement of ethanol metabolism in the rat liver using magnetic resonance spectroscopy of hyperpolarized [1-13C]pyruvate. 1952 98

The antioxidant activities of 53 medicinal plants used in Bamun folk medicine for the management of jaundice and hepatitis were investigated. The studies were done using rat hepatic microsomes for lipid peroxidation and bovine serum albumin (BSA) for carbonyl group formation. Silymarine was used as reference compound. Fifteen different extracts were effective at a dose of 200 microg/ml in both experiments. Specifically, 25 extracts inhibited lipid peroxidation initiated non-enzymatically by ascorbic acid while 18 inhibited peroxidation as determined by reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH). The inhibitory concentration 50 (IC(50)) of 23 different plant extracts was lower than 200 microg/ml in the microsomal lipid peroxidation inhibition study. Fifteen of the 23 extracts were active in preventing protein oxidation by inhibiting the formation of the carbonyl group on BSA with an IC(50) value less than 200 microg/ml. The results suggest that the antioxidant activity of the extracts, may be due to their ability to scavenge free radicals involved in microsomal lipid peroxidation or in protein oxidation. These biochemical processes are involved in the aetiology of toxic hepatitis.
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PMID:Inhibition of microsomal lipid peroxidation and protein oxidation by extracts from plants used in Bamun folk medicine (Cameroon) against hepatitis. 2016 49


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