Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with hepatic injury have an increased incidence of gastric ulcers and erosions. In this study, the effect of D-galactosamine(GalN)-induced hepatitis on ethanol-induced gastric mucosal lesions and the protective effect of anti-ulcer agents in rats were examined. Subcutaneous injection of GalN (1 g/kg) remarkably increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities suggesting induction of hepatic injury. Gastric mucosal lesions induced by ethanol were significantly aggravated in GalN-induced hepatitis rats. Orally administered ecabet (CAS 86408-72-2; 20-200 mg/kg) dose dependently inhibited ethanol-induced gastric mucosal lesions in GalN-induced hepatitis rats. Sucralfate (CAS 54182-58-0) tended to inhibit the gastric mucosal lesions at a dose of 200 mg/kg but teprenone (CAS 6809-52-5), cimetidine (CAS 51481-61-9) and rebamipide (CAS 90098-04-7) had little effect. All anti-ulcer agents had no effect on the serum ALT and AST activities increased by GalN pretreatment. These results indicate that the gastric mucosa of GalN-induced hepatitis rats is more susceptible to injury induced by luminal irritants such as ethanol. Ecabet potently inhibited gastric mucosal lesions suggesting its clinical utility for the gastric mucosal damage in patients with hepatic injury.
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PMID:Effects of anti-ulcer agents on ethanol-induced gastric mucosal lesions in D-galactosamine-induced hepatitis rats. 1223 47

Effects of dietary protein type on lipopolysaccharide (LPS)-induced hepatitis, as assessed by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, were investigated in D-galactosamine (GalN)-sensitized rats. The plasma ALT and AST activities in rats fed on 25% soybean protein isolate (SPI) diet were significantly suppressed to about 1/4 and 1/5 of the values in rats fed on 25% casein diet, respectively, 8 h after the injection of LPS + GalN. Although hepatic ALT and AST activities of normal rats were also lower in the SPI group than in the casein group, this could not explain the differences in plasma enzyme activities between the two groups. The hepatic glutathione concentration of normal rats was lower in the SPI group than in the casein group, but it was reversed in rats injected with drugs. The results suggest that SPI can protect animals from LPS + GalN-induced hepatitis, and that the hepatic glutathione level may participate in the effects of SPI.
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PMID:Differential effects of dietary casein and soybean protein isolate on lipopolysaccharide-induced hepatitis in D-galactosamine-sensitized rats. 1245 Jan 39

The role of high mobility group-1 protein (HMG-1) in LPS- and TNF-alpha-induced lethal shock in galactosamine (GalN)-sensitized mice was investigated. No detectable HMG-1 levels were observed by immunoblotting analysis in plasma from untreated or GalN-sensitized BALB/c mice 5 h after LPS injection, although significant levels of HMG-1 were detected in plasma 6 h after the challenge. All GalN-sensitized BALB/c but not BALB/lps(d) mice succumbed by 6 h after LPS injection. When GalN-sensitized mice were injected with TNF-alpha, the presence of HMG-1 was seen at 5.5 h in plasma of BALB/c mice and at 6 h in BALB/lps(d) mice, although almost all GalN-sensitized BALB/c mice died by 6 h after challenge. The time-dependent phenomenon correlated with elevated serum aspartate aminotransferase (AST) levels and the appearance of apoptotic cells in livers. Administration of pooled plasma, equivalent to approximately 200 microg recombinant murine HMG-1, taken from mice on the verge of near death, did not result in induction of lethal shock in GalN-sensitized mice. Taken together with the late appearance of HMG-1 in moribund mice, these data suggest that HMG-1 does not decisively contribute to lethality in the GalN sensitization model.
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PMID:Does high mobility group 1 protein function as a late mediator for LPS- or TNF-induced shock in galactosamine-sensitized mice? 1253 98

The aim of this study was to investigate the protective effect of honokiol and magnolol on hepatocyte injury induced by either tertiary butyl hydroperoxide (tBH)- or D-galactosamine (GalN). The cellular leakage of LDH and AST, and cell death by treatment with 1.5 mM tBH for 1 h, were significantly inhibited by treatment with honokiol (40 and 20 microM) or magnolol (40 microM). Treatment with honokiol or magnolol significantly inhibited lipid peroxidation in both cells and media, the generation of intracellular reactive oxygen species (ROIs), and intracellular glutathione (GSH) depletion induced by tBH. The cellular leakage of LDH and AST, and cell death, by 24-hour treatment with 30 mM GalN were significantly inhibited by treatment with honokiol (20, 5 and 1 microM) or magnolol (20, 5 and 1 microM). Treatment with honokiol (20, 5 and 1 microM) or magnolol (20 and 5 microM) significantly inhibited the intracellular GSH depletion induced by GalN. The hepatoprotective effects of honokiol and magnolol on oxidative stress induced by tBH were probably the result of their antioxidant activity. Honokiol and magnolol also had a protective effect against GalN-induced hepatotoxicity, which was used as an alternate model to oxidative stress, acting by inhibiting intracellular GSH depletion.
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PMID:Protective effects of honokiol and magnolol on tertiary butyl hydroperoxide- or D-galactosamine-induced toxicity in rat primary hepatocytes. 1256 76

The ability to document the extent of hepatic injury and predict the outcome of fulminant hepatic failure would be helpful in identifying those patients who might benefit from liver transplantation. The aim of the present study was to determine whether in vivo phosphorus-31 magnetic resonance spectroscopy (31P MRS) accurately assesses the severity of liver damage and is of prognostic value in a D-galactosamine (D-galN)-induced model of acute liver failure. Adult male Sprague-Dawley rats (n = 36) received an intraperitoneal dose of D-galN (1.0 g/kg), and MRS examinations were performed at peak (48 hours) and in subsequent experiments, just prior to peak (30 hours) hepatic injury. Rats not exposed to D-galN served as controls. The concentration of hepatic phosphorylated metabolites decreased in proportion to the severity of liver injury at 48 hours. Significant correlations were detected between hepatic adenosine triphosphate (ATP) and serum aspartate aminotransferase, bilirubin, and percentage of hepatocyte necrosis identified histologically (r = -.91, -.74, and -.92, respectively; p < .001). Prior to peak hepatic injury (30 hours), 31P MRS was able to predict with 100% accuracy those rats that would survive (ATP > 2.3 mM) and those that would not (ATP < 1.5 mM). When an intermediate cutoff value of 2.0 mM was selected, ATP levels were able to correctly predict survival and death with 80% and 60% accuracy, respectively. These findings indicate that hepatic ATP levels as measured by 31P MRS provide a noninvasive indication of the severity of liver damage and serve as a useful prognostic indicator of outcome in this model of acute liver failure.
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PMID:Utility of hepatic phosphorus-31 magnetic resonance spectroscopy in a rat model of acute liver failure. 1258 Mar 20

Daily, light ethanol consumption enhances hepatic regeneration following 70% partial hepatectomy in rats. Whether such consumption has a beneficial effect on the outcome following toxin-induced acute hepatitis has yet to be determined. One hundred ten adult male Spragne-Dawlay rats (200-250 g) were randomized to receive daily gavages with ethanol 1.0 g/kg (light ethanol group), 3.0 g/kg (moderate-heavy ethanol group), or an equal volume of tap water (controls). On day 30, a single injection of D-galactosamine hydrochloride (1.0 g/kg) (D-gal), a potent hepatotoxin that induces liver failure within 24-48 hr, was administered intraperitoneally. Gavages were discontinued and rats killed (N = 4-6/group) on days 1, 3, 5, 7, and 10 after D-gal. Serum AST, bilirubin, and liver histology served to document the extent of liver injury and [3H] thymidine incorporation into hepatic DNA: hepatic regenerative activity. Compared to controls, peak serum AST levels were significantly decreased in the light (-40%, P < 0.05) and increased in the moderate-heavy (+32%, P < 0.05) ethanol groups. Serum bilirubin levels approximately doubled in the light ethanol group while increasing sixfold in the moderate-heavy and control groups (P < 0.05). Histologic evidence of hepatic injury (graded 0-IV) was limited in the light ethanol group, intermediate in controls, and most extensive in the moderate-heavy ethanol group (P < 0.05). Despite less hepatic injury, hepatic regeneration was similar in the light ethanol group compared to controls and significantly impaired in the moderate-heavy ethanol group (P < 0.01). In conclusion, the results of this study indicate that daily, light ethanol administration attenuates hepatic injury, improves hepatic function, and enhances hepatic regeneration following toxin-induced hepatitis in rats.
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PMID:Effects of daily, light and moderate-heavy ethanol exposure on extent of hepatic injury and recovery following toxin-induced acute hepatitis in rats. 1277 92

Holotrichia diomphalia larvae, one of the most widely used Korean folk medicinal preparations, have long been used for the treatment of chronic liver cirrhosis. The present study was undertaken to clarify whether extract of Holotrichia diomphalia larvae could prevent acute liver damage and liver fibrosis in rats. A single administration of Holotrichia diomphalia protected rats from acute liver damage induced by carbon tetrachloride (200 micro l/kg, i.p.) and beta-D-galactosamine (600mg/kg, i.p.). This was evidenced by the lowered serum aminotransferase (ALT, AST) activities in rats treated with Holotrichia diomphalia. The hepatic cirrhosis was induced by 28 days of bile duct ligation/scission in rats. The four-week treatment with Holotrichia diomphalia reduced the serum ALT, AST, alkaline phosphatase activities, and hydroxyproline content in the liver and improved the histological appearance of the liver sections. The present results led us to conclude that Holotrichia diomphalia larvae can reduce the degree of hepatocellular damage and may become a promising antifibrotic agent for liver fibrosis/cirrhosis.
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PMID:Effect of Holotrichia diomphalia larvae on liver fibrosis and hepatotoxicity in rats. 1286 Mar 4

A hallmark of tumorigenesis is resistance to apoptosis. To explore whether resistance to cell death precedes tumor formation, we have studied the short-term effects of the hepatocarcinogen 2-acetylaminofluorene (AAF) on liver mitochondria, on hepatocytes, and on the response to bacterial endotoxin lipopolysaccharide (LPS) in albino Wistar rats. We show that after as early as two weeks of AAF feeding liver mitochondria developed an increased resistance to opening of the permeability transition pore (PTP), an inner membrane channel that is involved in various forms of cell death. Consistent with a mitochondrial adaptive response in vivo, (i) AAF feeding increased the expression of BCL-2 in mitochondria, and (ii) hepatocytes isolated from AAF-fed rats became resistant to PTP-dependent depolarization, cytochrome c release, and cell death, which were instead observed in hepatocytes from rats fed a control diet. AAF-fed rats were fully protected from the hepatotoxic effects of the injection of 20-30 microg of LPS plus 700 mg of d-galactosamine (d-GalN) x kg-1 of body weight, a treatment that in control rats readily caused a large increase of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive cells in liver cryosections and release of alanine and aspartate aminotransferase into the bloodstream. Treatment with LPS and d-GalN triggered cleavage of BID, a BCL-2 family member, in the livers of both control- and AAF-fed animals, whereas caspase 3 was cleaved only in control-fed animals, indicating that the mitochondrial proapoptotic pathway had been selectively suppressed during AAF feeding. Phenotypic reversion was observed after stopping the carcinogenic diet. These results underscore a key role of mitochondria in apoptosis and demonstrate that regulation of the mitochondrial PTP is altered early during AAF carcinogenesis, which matches, and possibly causes, the increased resistance of hepatocytes to death stimuli in vivo. Both events precede tumor formation, suggesting that suppression of apoptosis may contribute to the selection of a resistant phenotype, eventually increasing the probability of cell progression to the transformed state.
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PMID:Early resistance to cell death and to onset of the mitochondrial permeability transition during hepatocarcinogenesis with 2-acetylaminofluorene. 1290 2

The aim of this study was to evaluate the effect of insulin-like growth factor-I (IGF-I) on lethality and liver function in experimental acute liver failure. Intravenous co-administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) to rats induced high mortality and marked increases in aspartate aminotransferase, alanine aminotransferase and total bilirubin, associated with hypoglycemia. One-hour pre-treatment with IGF-I significantly prevented lethality and blood parameter changes in rats. Histological examination also showed that massive hepatocellular hemorrhagic necrosis and inflammatory cell infiltration around peri-central veins in the liver, as well as shrinkage of cytoplasm and nuclear condensation, were induced by GalN plus LPS injection, but these all were improved by pre-treatment with IGF-I. Overall, this study showed that IGF-I treatment resulted in effective prevention of lethal acute liver failure in rats induced by GalN plus LPS, suggesting a therapeutic potential for IGF-I in the prevention of acute liver failure.
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PMID:Insulin-like growth factor-I prevents lethal acute liver failure induced by D-galactosamine and lipopolysaccharide in rats. 1292 83

In rodents, submandibular salivary glands accumulate a number of biologically active peptides, and release some of them to both saliva and the bloodstream. Surgical removal of these glands (sialoadenectomy) alters the ability of the liver to regenerate after partial hepatectomy. We show here that 5 weeks after surgery, the liver of sialoadenectomized mice contained 40% fewer hepatocytes than the liver of sham-operated mice. We did not obtain evidence of necrotic cell death after surgery. In contrast, sialoadenectomy transiently increased apoptotic hepatocyte death, as revealed by terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling (TUNEL) assay. DNA synthesis was determined in vivo by the incorporation of bromo-deoxyuridine (BrdU) into hepatocyte nuclei. BrdU-labeling progressively increased after sialoadenectomy. We conclude that sialoadenectomy induced a transient wave of apoptotic cell death followed by a rise in DNA synthesis but not by cell division. This reduced cell number but increased mean cell volume. In spite of these alterations in cellularity, the liver responded adequately to several stressful conditions, as judged by the lack of any differential effect of sialoadenectomy on liver glycogen and plasma glucose concentration after immobilization, aggressive encounter, or fasting. However, the liver of sialoadenectomized mice was more sensitive to the effect of a non-lethal dose of bacterial lipopolysaccharide (LPS) combined with d-galactosamine, as shown by the enhanced rise in plasma alanine aminotransferase and aspartate aminotransferase, and liver myeloperoxidase (MPO) activities. All these results indicate that a submandibular salivary glands-liver axis is involved in the maintenance of liver structure in mice. A disturbance of this axis induces an adaptive response that preserves the metabolic function of the liver but renders it more sensitive to bacterial endotoxins.
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PMID:Sialoadenectomy alters liver cell turn-over and function in mice. 1458 39


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