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)

Simultaneous intraperitoneal administration of 700 mg/kg galactosamine and 33 micrograms/kg Salmonella abortus equi endotoxin to male NMRI albino mice resulted in fulminant hepatitis as assessed after nine hours by measurement of serum transaminases as well as sorbitol dehydrogenase activities. Intraperitoneal pretreatment of animals with 2 X 100 mg/kg allopurinol, or intravenous pretreatment with 33 kU superoxide dismutase or 1 MU catalase fully prevented hepatitis. Administration of 10 micrograms/kg of the prostacyclin analogue iloprost antagonized liver injury when given simultaneously with galactosamine/endotoxin but did not protect when given 90 min later. Tocopherol or desferal pretreatment of the animals had no significant protective effect. Together with our recent finding that hepatic leukotriene D4 production is likely to be responsible for galactosamine/endotoxin-induced hepatitis we interpret these results as evidence for a leukotriene-induced hepatic ischemia followed by a reperfusion syndrome.
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PMID:Evidence for the involvement of a reperfusion injury in galactosamine/endotoxin-induced hepatitis in mice. 360 63

Oral pretreatment with greater than 1 mg/kg ebselen protected Wistar rats from shock induced by 20 mg/kg endotoxin when heart stroke volume after 60 min. was taken as a measure. Similarly, the drug protected male NMRI mice sensitized by 700 mg/kg galactosamine and treated with 33 micrograms/kg endotoxin against fulminant hepatitis assessed by transaminases release after nine hours. The validity of the model was checked by administration of drugs interfering with arachidonate metabolism. Chemical depletion of hepatic glutathione resulted in an apparent protection from galactosamine/endotoxin shock in mice. It is concluded that peptido-leukotrienes are likely to be responsible for the manifestation of this pathophysiological condition.
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PMID:Protection by ebselen against endotoxin shock in rats or mice sensitized by galactosamine. 361 36

Although copper is believed to be hepatotoxic in Wilson's disease and Indian Childhood Cirrhosis (ICC), the rat shows only minimal hepatic damage on copper-loading. To investigate the possibility that copper deposition may potentiate the effects of a superimposed hepatitis, D-galactosamine (GalN) was given to copper-loaded and control rats. In the non-copper-dosed rats, GalN 0.85 g/kg i.p. produced elevated serum AST (3731 +/- 545 IU/l; normal 64.8 +/- 2.1), ALT (2090 +/- 190 IU/l; normal 18.0 +/- 0.7), and OCT (16.7 +/- 2.6 mmol/min/ml; normal 0.12 +/- 0), and liver cell necrosis with portal infiltration. In rats whose liver copper was elevated to 1298 +/- 169 micrograms/g (control 18.7 +/- 1.7) by oral copper supplementation, GalN produced much smaller increases in AST (825 +/- 122 IU/l), ALT (103 +/- 15 IU/l) and OCT (0.27 +/- 0.02 mmol/min/ml) and minimal histological damage. Viable bacterial cell counts from faecal homogenates showed that the anaerobically cultured bacteria were reduced on copper-dosing of rats. Therefore the protective effect of copper may be due to a decrease in gut-derived endotoxin acting on the liver, or to an impaired prostaglandin synthesis or perhaps to synthesis of acute phase reactants.
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PMID:Copper protects against galactosamine-induced hepatitis. 365 8

High levels of acute phase proteins (acute phase reactants, APR) suppress acute inflammatory reactions in the rat. As many APR have antiprotease properties, including an anticollagenase activity, the effect of APR on the development of CCl4-induced liver fibrosis was investigated in rats. APR were provoked by repeated injections of epinephrine, inducing a broad spectrum of APR. This reaction can be monitored measuring alpha 2-macroglobulin levels in the rat (alpha 2-macrofetoprotein, alpha M FP). This protein was found to inhibit both acute galactosamine hepatitis and acute CCl4-induced liver toxicity. The animals with high levels of APR at the start of CCl4 treatment developed a more severe degree of fibrosis and cirrhosis than the control group in which no acute phase reaction was induced. Epinephrine alone had no such effects. Additionally, the APR positive group showed an initially lower degree of hepatocellular damage when compared to control animals. This uncoupling of liver cell damage and subsequent fibrosis may demonstrate that higher levels of APR might be important as to the development of cirrhosis, possibly based on the anticollagenase activity of these proteins.
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PMID:Acute phase reactants enhance CCl4 induced liver cirrhosis in the rat. 369 34

The spontaneous course of the galactosamine-hepatitis in the guinea-pig (750 and 1000 mg/kg GalN iv respectively) is characterized by a terminal hypoglycemia together with hypothermia and arterial hypotension fifty-nine hours on average after GalN-application. Preventing hypoglycemia and hypothermia by continuous intravenous infusion of a glucose solution and by increasing room temperature, the animals do not develop hepatic coma, but show an increasing disturbance of the righting reflex and survive at least seventy-two hours. Plasma biochemical tests and liver histology reflect severe hepatic damage. A twofold increase of the liver weight is caused by raised water and lipid content combined with a concomitant depletion of liver glycogen. Pharmacological studies with 14C-Pentobarbital result in a distinctly diminished clearance and in a prolonged half life while the cytochrome P-450 content of the liver shows a moderate decrease. In animal models of acute liver failure the possible incidence of hypoglycemia, arterial hypotension and hypothermia should be considered.
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PMID:[Galactosamine-induced acute liver failure in the guinea pig--spontaneous course and controlled study conditions]. 371 20

Male albino NMRI mice were given 700 mg/kg galactosamine and 33 micrograms/kg salmonella endotoxin intraperitoneally. After 9 hr, serum sorbitol dehydrogenase activity had risen from 60 to 7320 U/l, SGOT from 90 to 5580, and SGPT from 70 to 10,440. When a similar dose of galactosamine alone or endotoxin alone was given, no significant liver injury was found. Animals pre-treated with an oral dose of ebselen (600 mg/kg 1-3 hr before galactosamine/endotoxin administration) were fully protected against this type of hepatitis. When pretreated 1 hr before intoxication with different doses of ebselen, significant dose-dependent reduction of serum enzyme activities was observed at doses higher than 1 mg/kg. After pre-treatment with 6 mg/kg ebselen, no biochemical or histological signs of liver lesions were detectable 36 hr after intoxication. In order to comparatively evaluate the model used, several established anti-inflammatory drugs were administered at doses which showed 50% effectiveness in preventing carageenan paw edema. A dose of 200 micrograms/kg dexamethasone, or 9 mg/kg indomethacin abolished galactosamine/endotoxin-induced enzyme release in our animals, as did the lipoxygenase pathway inhibitor diethylcarbamazine (78 mg/kg). In contrast, administration of cyclooxygenase pathway inhibitors such as aspirin (220 mg/kg) or ibuprofen (45 mg/kg) failed to prevent hepatitis. The effect of ebselen was also investigated in four different models of acute drug-induced liver damage. A dose of 600 mg/kg of the organic selenium compound was ineffective or weakly active in benzo(alpha)pyrene- or phenobarbital-treated mice which were intoxicated by intraperitoneal administration of 350 or 400 mg/kg body weight of paracetamol. Similarly negative results were obtained against bromobenzene-induced hepatotoxicity (520 mg/kg bromobenzene i.p.), carbon tetrachloride intoxication (3.2 g/kg), or allyl alcohol-induced liver damage (60 mg/kg). The selective efficacy of ebselen against galactosamine/endotoxin induced liver damage is interpreted in terms of its recently recognized ability to inhibit the formation of leukotrienes.
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PMID:A novel biologically active seleno-organic compound--VI. Protection by ebselen (PZ 51) against galactosamine/endotoxin-induced hepatitis in mice. 372 68

Brain edema and intracranial hypertension are major complications of fulminant hepatic failure. We investigated the development of brain edema and monitored intracranial pressure in rabbits with toxic hepatitis induced by galactosamine. Using a gravimetric technique to assay small tissue samples, we found that brain water was increased in cortical grey matter, but not in subcortical, mesencephalic, and pontine white matter, or in the cerebellum. The proportion of water in cerebral grey matter in control animals was 80.96% +/- 0.49% with significant elevations to 81.96% +/- 0.47% and 82.95% +/- 1.49% in mild and severe encephalopathy, respectively. This corresponds to mean increases in tissue volume of 5.5% and 11.7%. The hippocampal grey matter also accumulated water in severe encephalopathy with a 30% increase in mean tissue volume. The regional increase in brain water was confirmed by the wet-dry weight method. Neither hypotension, hypoxia, nor severe hypoglycemia were present to account for the edema. Intracranial pressure was monitored continuously in unanesthetized rabbits via an intraventricular cannula as encephalopathy developed. The pressure was normal in the mild stage, but was intermittently elevated in animals with severe encephalopathy. The normal range of intracranial pressure was 2-9 mmHg and the range of peak values in galactosamine-treated rabbits was 18-55 mmHg. The regional differences in brain water accumulation suggest that cellular swelling and abnormalities in the movement of water across the blood-brain barrier may account for the brain edema in this model.
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PMID:Brain edema in rabbits with galactosamine-induced fulminant hepatitis. Regional differences and effects on intracranial pressure. 377 Mar 59

Lipid molecules in lipoprotein surfaces exchange with their counterparts in cell plasma membranes. In human or experimental liver disease, plasma lipoprotein surfaces are enriched in cholesterol and deficient in arachidonate; corresponding alterations occur in membrane lipids of erythrocytes. To determine whether similar changes take place in membranes of nucleated cells, the lipid content of plasma and of erythrocyte, liver and kidney membranes was measured in rats with acute (3-day) galactosamine-induced hepatitis or chronic (3-week) biliary obstruction. In both models of liver injury the cholesterol:phospholipid ratio in plasma and in erythrocytes was significantly increased (P less than 0.001). Although this ratio was also elevated in liver and kidney microsomes, only in liver microsomes of obstructed rats was the increase significant (P less than 0.001). However, the cholesterol:phospholipid ratio of kidney brush-border membranes, was significantly higher in bile-duct-ligated rats; presumably, compensating mechanisms limit cholesterol accumulation in intracellular membranes. Kidney brush-border membranes from obstructed rats were deficient in arachidonate as were plasma and erythrocytes. However, arachidonate levels were unchanged in kidney microsomes; renal delta 6-desaturase, the rate-limiting enzyme in the conversion of linoleic acid to arachidonic acid, was increased by 50% (P less than 0.001) and may have counteracted a reduced supply of exogenous lipoprotein arachidonate. We conclude that in experimental liver disease lipoprotein-induced lipid abnormalities can occur in renal membranes, although compensatory mechanisms may operate; the alterations seen, cholesterol accumulation and arachidonate depletion, would be expected to interfere with sodium transport and prostaglandin production, respectively. Our findings support the hypothesis that lipid abnormalities in kidney membranes contribute to the renal dysfunction which is a frequent complication of human liver disease.
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PMID:Membrane lipid changes in erythrocytes, liver and kidney in acute and chronic experimental liver disease in rats. 379 May 85

Hepatitis was induced in rabbits by a single intraperitoneal injection of D(+)-galactosamine-HCl (750 mg/kg body wt). Plasma lecithin:cholesterol acyltransferase activity fell to 5% and lipid transfer protein activity to 50% of control values 48 hr after injection. Discoid high density lipoprotein began to appear in plasma of treated rabbits 36 hr after injection, along with populations of high density lipoprotein (HDL) which were both smaller (radius 3.7 nm) and larger (radius 5.9 nm) than the original HDL population (radius 4.8 nm).
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PMID:D-galactosamine induced hepatitis in the rabbit: effect on lecithin:cholesterol acyltransferase activity, plasma lipid transfer protein activity and high density lipoproteins. 379 65

The present study was carried out to examine the effect of single or consecutive administration of T-2588 on liver of male rat injured by the administration of D-galactosamine X HCl. The T-2588 was orally given to hepatic-injured rats at doses of 125 mg/kg and 1,000 mg/kg singly or for consecutive 5 days. A 10 ml/kg dose of the vehicle was orally given to control rats. The results obtained were summarized below. Single administration of T-2588. Twenty-four hours after a single administration of T-2588, the liver taken from control rats apparently indicated galactosamine-induced hepatitis. No drug-related alterations were observed in hepatic functional test, liver weight and histological examinations at either dose of T-2588. Galactosamine-induced hepatitis was not affected by a single administration of T-2588. Consecutive administration of T-2588. Twenty-four hours after a 5-consecutive-day administration of T-2588, galactosamine-induced hepatitis in control rats was restored to the normal state. The cure of galactosamine-induced hepatitis was not affected by a 5-consecutive-day administration of T-2588. The hepatic aldehyde dehydrogenase activity in hepatic-injured rats was not affected by a 5-consecutive-day administration of T-2588.
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PMID:[Effect of single or consecutive administration of T-2588 on hepatic-injured male rats]. 379 80


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