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)

Dimethyl diphenyl bicarboxylate (dimethyl-4,4'-dimethyloxy-5,6,5',6'-dimethylene-dioxy-di phe nyl-2,2'- bicarboxylate, DDB), a synthetic mimic of the natural product schizandrin C, is used in China as a hepatoprotective agent to improve the liver functions of patients with hepatitis or under cancer chemotherapy. In this study, we investigated the effects of DDB on liver microsomal drug-metabolizing enzymes. When male Sprague-Dawley rats were treated with a daily intragastric dose of DDB (200 mg.kg-1) for 3 d, the microsomal pentoxyresorufin dealkylase activity and P-450 2B1 protein levels were markedly increased. The fold increase was lower than that by phenobarbital (75 mg.kg-1, ip once daily x 3 d). The level of P-450 2B1 mRNA was elevated by DDB but the magnitude of the elevation was much less than that caused by phenobarbital. DDB also increased the rates of testosterone hydroxylation at positions 16 beta, 16 alpha, 6 beta, and 2 beta as well as the rate of ethoxyresorufin dealkylation, suggesting moderate increases in the levels of P-450 3A and P-450 1A1 in addition to the huge increase in P-450 2B1. The level of glutathione S-transferase was also slightly increased, but the levels of P-450 2E1 and NAD(P)H: quinone oxidoreductase were not changed. The results indicate that DDB is an inducer of P-450 2B1.
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PMID:Induction of liver microsomal cytochrome P-450 2B1 by dimethyl diphenyl bicarboxylate in rats. 130 34

Arthralgia and arthritis may be one of the early signs of hepatic diseases. Comparison of the course of the articular syndrome with the biochemical and immunological data (cationic proteins, NAD, NADP, antigenic markers of viral hepatitis, T lymphocyte subpopulations, and so forth) allowed one to establish a relationship between the parameters studied, to define an important role they play in early diagnosis of liver injuries, in predicting the course of the autoimmune process in active hepatitis. Extracorporeal methods of treatment for chronic hepatic diseases are an important prophylactic and therapeutic factor in the correction of pathogenetic alterations underlying the diseases.
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PMID:[Reactive arthritis in liver diseases]. 188 19

Galactosamine, a selective hepatotoxin, produces in rats histologic alterations, which show the characteristics of severe human viral hepatitis. In the present study the efficacy of two different cofactor regimens (coenzyme A, NAD, alpha lipoic-acid, cocarboxylase) in rats with fulminant galactosamine hepatitis were tested. The results showed an improvement of the short-term survival with a short-term treatment and definitely better survival with a long-term regimen with cofactors.
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PMID:Effect of coenzyme-A, NAD, alpha lipoic-acid and cocarboxylase on survival of rats with galactosamine-induced severe hepatitis. 392 31

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

1. The effects of racemic thalidomide (D[+]/L[-] alpha-phthalimido-glutarimide) on acetaminophen (AAP)-induced hepatitis were tested in male NMRI mice (n = 133) and quantified as serum activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT). 2. A 2.1-fold increase of GOT and a 1.9-fold increase of GPT activities (P < 0.001) were observed in mice treated perorally with 500 mg/kg of AAP plus 150 mg/kg of thalidomide (Thal). In the absence of AAP, Thal did not display any detectable hepatotoxic effects. 3. The Thal-induced exacerbation of AAP hepatotoxicity was completely inhibited by nicotinic acid amide, a selective inhibitor of poly(ADP-ribose) polymerase (PARP) (P < 0.0001), suggesting a possible influence of Thal on the hepatic metabolism of NAD-adenoribosylation. 4. We see the main application of nicotinic acid amide as for the combinational use in pharmaceutical preparations of AAP in order to avoid hepatic damage in patients treated with AAP and Thal.
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PMID:Exacerbation of acetaminophen hepatotoxicity by thalidomide and protection by nicotinic acid amide. 759 Jan 13

Recently, we demonstrated the hepatoprotective effects of nicotinic acid amide, a selective inhibitor of poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) on mice suffering from acetaminophen (AAP)-hepatitis, suggesting that the AAP-induced liver injury involves a step which depends on adenoribosylation. The present study investigates the effects of a diet free of precursors of NAD, the substrate on which PARP acts, in female NMRI mice with AAP hepatitis and evaluates the influence of simultaneous ethanol consumption in these animals. Liver injuries were quantified as serum activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT). While AAP caused a 117-fold elevation of serum transaminase activities in mice kept on a standard laboratory diet, which was significantly exacerbated by ethanol and inhibited by nicotinic acid amide (NAA), adverse effects were noted in animals fed a diet free of precursors of NAD. In these animals, only minor increases of serum transaminase activities were measured in the presence of AAP, and unlike the exacerbation caused by ethanol in mice on a standard diet, the liver damage was inhibited by 50% by ethanol. A further 64% reduction of hepatitis was observed, when NAA was given to ethanol/AAP-mice. Our results provide evidence that the AAP-induced hepatitis and its exacerbation by ethanol can either be reduced by end-product inhibition of PARP by NAA or by dietary depletion of the enzyme's substrate NAD. We see the main application of NAA as for the combinational use in pharmaceutical preparations of acetaminophen in order to avoid hepatic damage in patients treated with this widely used analgesic.
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PMID:Influence of diet free of NAD-precursors on acetaminophen hepatotoxicity in mice. 874 98

Correcting action of vitamin E and it's short chain derivative on the activity of some mitochondria electron transport chain enzymes were investigated on models of acute and chronic toxic hepatitis. Inhibition of NADH- and succinate-cytochrome c oxidoreductase complexes activity was established in short term action of xenobiotics. Treatment of rats with CCl4 during 60 days lowered activity of NADH-cytochrome c oxidoreductase complex and significantly increased activity of succinate-cytochrome c oxidoreductase complex and succinate dehydrogenase. Obviously, as a result of long term influence of hepatotoxic agents switching over in rat mitochondria electron transport from NAD-dependent way of substrate oxidation to succinate-dependent way took place. This event could be a part of the body adaptation mechanisms. Vitamin E and its short chain analogue corrected activities of investigated enzymes of mitochondria liver in the animals with acute and chronic hepatitis.
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PMID:[Correction of the activity of certain enzymes in the rat liver mitochondrial electron transport chain by derivatives of alpha-tocopheryl acetate in toxic damage to the liver]. 1079 Oct 53

Disulfiram (Ds), a clinically employed alcohol deterrent of the thiuram disulfide (TD) class of compounds, is known to cause hepatitis and neuropathies. Although this drug has been shown to inhibit different thiol-containing enzymes, the actual mechanism of Ds toxicity is not clear. We have previously demonstrated that Ds impairs the permeability of inner mitochondrial membrane (IMM) [Arch. Biochem. Biophys. 356 (1998) 46]. In this report, the effect of Ds and its structural analogue thiram (Th) on mitochondrial functions was studied in detail. We found that mitochondria metabolize TDs in a NAD(P)H- and GSH-dependent manner. At the concentration above characteristic threshold, TDs induced irreversible oxidation of NAD(P)H and glutathione (GSH) pools, collapse of transmembrane potential, and inhibition of oxidative phosphorylation. The presence of Ca(2+) and exhaustion of mitochondrial glutathione (GSH+GSSG) decreased the threshold concentration of TDs. Swelling of the mitochondria and leakage of non-transported fluorescent dye BCECF from the matrix indicated that TDs induced the mitochondrial permeability transition (MPT). Mitochondrial permeabilization by TDs involves two, apparently distinct mechanisms. In the presence of Ca(2+), TDs produced cylosporin A-sensitive swelling of mitochondria, which was inhibited by ADP and accelerated by carboxyatractyloside (CATR) and phosphate. In contrast, the swelling produced by TDs in the absence of Ca(2+) was not sensitive to cyclosporin A (CsA), ADP and CATR but was inhibited by phosphate. Titration with N-ethylmaleimide revealed that these two mechanisms involve different SH-groups and probably different transport proteins on the IMM. Our findings indicate that at pharmacologically relevant concentrations TDs may cause an irreversible mitochondrial injury as a result of induction of the MPT.
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PMID:Mitochondrial injury by disulfiram: two different mechanisms of the mitochondrial permeability transition. 1171 85

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

Experimental toxic hepatitis is accompanied by a decrease of 6-phosphogluconate dehydrogenase (6PGD, 1.1.1.44) activity in rat liver. Enzyme preparations of 6PGD, obtained from livers of control group rats and animals with toxic exhibit the same molecular mass of 114.2 +/- 5.8 kDa. However G6PD isolated from liver of animals with toxic hepatitis exhibited altered Km and pH-optimum values. Reduced glutathione inhibited 6PGD-activity from the liver of control group rats and did not affect the enzyme from liver of animals with toxic hepatitis. Inhibition effect of oxidized glutathione is stronger in the pathological state. Malate, citrate, 2-oxoglutarate and isocitrate activated the enzyme from control animals, but did not the enzyme isolated from animals with hepatitis. Regulation of 6PGD-activity from liver of control and experimental animals by some nucleotides (NAD, ADP, AMP) and ribose-5-phosphate was also different.
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PMID:[Catalytic properties of 6-phosphogluconate dehydrogenase from rat liver in normal state and during toxic hepatitis]. 1718 Sep 22


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