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)

The effects of allyl alcohol, galactosamine, bromobenzene, and corn oil administration were evaluated in male Fischer 344 rats at 4 to 5, 14 to 15, and 24 to 25 months of age to determine if susceptibility to hepatotoxic injury is modified as a consequence of aging. Parameters measured were (1) severity of hepatocellular necrosis as judged by light microscopy of liver sections, (2) activity of alanine aminotransferase and aspartate aminotransferase in serum, and (3) hepatic microsomal cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity. Allyl alcohol toxicity was more severe in middle-aged and old rats than in young-adult rats. In contrast, galactosamine and bromobenzene toxicities were slightly decreased or unchanged in old rats. The results demonstrate that aging has effects on some types of chemically induced hepatotoxicity.
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PMID:Influence of aging on the susceptibility of rats to hepatotoxic injury. 671 May 24

Effects of halothane anesthesia were investigated in ponies prepared surgically with chronic external biliary fistulas (T tubes) to determine the effects on liver function and biliary excretion during 2 hours of anesthesia. Four studies were performed on 2 ponies, 2 to 6 months after surgery with the enterohepatic circulation held intact between studies. Intravenous bile acid infusion was used to maintain steady-state bile flow, bilirubin, and bile acid excretion during each study. Compared with the immediate 2-hour preanesthesia values (base line), halothane caused a 138% increase in bilirubin excretion, a 60% increase in biliary bilirubin concentration, and a 43% increase in PCV. Halothane anesthesia also caused a 16% reduction in plasma bilirubin, a 46% reduction in biliary bile acid concentration, and a 27% reduction in bile acid excretion. The bile acid independent fraction of bile flow appeared to increase. Plasma aspartate transaminase concentration did not change during anesthesia. The ratio of conjugated bilirubin fractions in bile [82% to 83% disconjugates of glucuronide and glucoside (2 forms) and 17% to 18% monoconjugates of glucoside, glucuronide, and xyloside] did not change during anesthesia and less than 1% was excreted unconjugated. Halothane anesthesia did not appear to affect adversely the activity of the transferase-conjugating enzymes in the presence of an increased bilirubin load. Seemingly, greatly increased conjugated bilirubin excretion observed during halothane anesthesia was most likely the result of a combination of increased hepatic clearance from plasma and increased hepatic bilirubin production from turnover of free hepatic heme or heme from the induced cytochrome P-450 system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of halothane anesthesia on equine liver function. 673 75

Prior consumption of a diet containing the food antioxidant, butylated hydroxyanisole (BHA), by female mice prevented the development of or minimized the acute liver damage caused by monocrotaline, acetaminophen, or bromobenzene. In contrast, neither the incidence nor the severity of carbon tetrachloride-induced hepatotoxicity was affected by dietary BHA. Hepatotoxicity was judged by plasma alanine aminotransferase and aspartate aminotransferase levels, hepatic cytochrome P-450 content, and liver histology. The protective effect of BHA against acetaminophen-induced hepatotoxicity was not demonstrated in male mice. The observed protection by dietary BHA against acetaminophen- and bromobenzene-induced hepatotoxicity was associated with the increase of liver glutathione. It is concluded that the protective action of BHA is dependent upon the nature of the toxic agent.
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PMID:Protective role of dietary butylated hydroxyanisole against chemical-induced acute liver damage in mice. 685 90

The hepatotoxic effect of carbon tetrachloride (CCl4), reflected by augmented blood aspartate aminotransferase and alanine aminotransferase activities and the extent of histological liver damage, was observed following oral administration of CCl4 to rats. A marked increase of blood transaminase activities and severe degeneration of hepatocytes in the centrilobular region were detected 1-2 days after the administration, while the cytochrome P-450 content and the drug metabolizing activity in livers were depressed immediately after the administration. Based on these results, the effect of CCl4 on hepatic cytochrome P-450 and the histological pattern of liver cells was observed using tissue samples obtained from various liver lobes of rats given CCl4 24 hr previously. Dose-dependent inactivation of cytochrome P-450 by the administration of CCl4 was observed throughout the liver, with the most extensive decrease in the cytochrome content in the median lobe. The extent of liver damage (hydropic swelling degeneration and central necrosis in lobule) was also greater in the median and right liver lobes than in the left lobe. When a small amount of CCl4 was administered, degeneration of liver cells was detected only in the median and right lobes with only slight degeneration in the left lobe. These results indicate different susceptibilities of rat liver lobes to CCl4.
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PMID:Carbon tetrachloride-induced hepatotoxicity in rats: evidence for different susceptibilities of rat liver lobes. 688 48

Ticrynafen, a uricosuric diuretic agent which causes hepatocellular injury in man as an apparent idiosyncratic reaction, was found to impair the function of the isolated perfused rat liver. At concentrations in the perfusate equivalent to those produced in the blood of man by therapeutic doses, the drug led to a striking reduction in bile flow and sulfobromophthalein excretion and release of aspartate aminotransferase into the perfusate. These adverse effects were enhanced by treatment of rats with phenobarbital prior to removal of the liver, indicating that the adverse effect of ticrynafen is probably caused by a metabolite produced in the cytochrome P-450 system.
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PMID:Effects of ticrynafen on hepatic excretory function in the isolated perfused rat liver. 706 19

The influence of Zn on the acute hepatotoxicity of pyrrolizidine alkaloids (PAs) was determined in male rats. Zinc, 72 mumol/kg as ZnCl2, was administered ip for 3 consecutive days, followed 16 h after the last dose by a single ip injection of purified mixed PAs (80, 120, or 160 mg/kg) obtained from tansy ragwort (Senecio jacobaea). Hepatotoxicity of the PAs was assessed by measuring the activities of plasma glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) and by histological examination of the liver. There was a dose-dependent increase in plasma GOT and GTP 24 h after PA administration, whereas no significant increase of these enzymes was seen after administering Zn alone. The 7-fold increase in plasma GOT and 12-fold increase in GPT after PA (120 mg/kg) were reduced to 2.4- and 2.1-fold, respectively, by Zn pretreatment. The PA-induced liver necrosis was either reduced in severity or abolished by Zn when the PA dose was 80 or 120 mg/kg. These results suggest a protective effect of Zn against PA hepatotoxicity. The protective effect was associated with a marked increase in liver metallothionein and a significant decrease in hepatic cytochrome P-450 content, aminopyrine N-demethylase activity, and in vitro microsomal conversion of the PAs to pyrroles. Liver nonprotein sulfhydryls were unchanged. The possible role of metallothionein in the sequestration of pyrrole metabolites merits further investigation.
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PMID:Protective action of zinc against pyrrolizidine alkaloid-induced hepatotoxicity in rats. 709 90

Administration of a single high dose of styrene (878 mg/kg ip in corn oil) to young male rats produced significant elevations in the activities of serum transaminases: 230, 209, and 71% increases in the activity of serum glutamic-oxaloacetic transaminase (SGOT) and 163, 437, and 227% in that of serum glutamic-pyruvic transaminase (SGPT) at 2, 6, and 24 h, respectively, after the dose. These results demonstrated that styrene could produce acute hepatic injury in young rats. Urinary nonprotein sulfhydryl contents and mandelic, phenylglyoxylic, and hippuric acids were all increased. Pretreatment of rats with phenobarbital and 3-methylcholanthrene did not further enhance the activities of SGOT and SGPT after styrene, but produced changes in other biochemical parameters, for example, an increase in liver weight, decrease in serum albumin and globulin concentrations, increase in serum alkaline phosphatase activity at 2 and 6 h, and increase in urinary urobilinogen concentrations. In addition, such pretreatments further increased the nonprotein sulfhydryl contents at 2 and 6 h after styrene injection. Pretreatment of rats with the microsomal enzyme inhibitor SKF 525-A failed to prevent the hepatotoxicity induced by styrene and did not modify the overall urinary excretion profiles of styrene metabolites. This study suggests that the mechanism of the activation/deactivation process leading to the metabolism and hepatotoxicity of styrene is complex and that alternative pathways not dependent on cytochrome P-450 might also be involved.
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PMID:Effects of microsomal induction and inhibition on styrene-induced acute hepatotoxicity in rats. 733 32

Our previous studies showed that polybrominated biphenyl (PBB) induced hepatic microsomal cytochrome P-450 in dairy cattle but did not elevate hepatic cytosolic ornithine decarboxylase or serum isocitrate dehydrogenase. These enzymes would be expected to increase during hepatotoxic injury and regeneration. Thus, PBB appeared to be a hepatotoxin in rats but not in cattle. In order to identify and confirm the response capability of bovine liver to hepatotoxins, we administered thioacetamide, a hepatotoxin known to induce hepatonecrosis, to a dairy calf. A progression of clinical signs of toxicosis was evident until the animal was moribund by 23 hr postdosing. Histolopathologic alterations in the liver included centrilobular necrosis with congestion and subcapsular microhemmorrhage. Marked changes in serum protein profiles were not noted. However, distinct increases in serum Fe and bilirubin occurred with progressing toxicosis, as did sharp declines in glucose and triglycerides. Serum lactic dehydrogenase, alkaline phosphatase, glutamic-oxaloacetic transaminase, isocitrate dehydrogenase and glutamic-pyruvate transaminase were elevated. Elevation of ornithine decarboxylase was dramatic when compared to the level in normal fetal bovine liver. From studies of its kinetic properties, bovine liver ornithine decarboxylase appears to have an apparent Km for ornithine decarboxylase of .45 mM. Liver homogenates from PBB-treated animals did not form inhibitors to ornithine decarboxylase. Compared with the thioacetamide-treated calf, the normal adult bovine, pregnant adult and 6-month fetus had relative activities of .2 .4 and 5.8%, respectively. These studies show that ornithine decarboxylase is low in liver of normal cattle, but is elevated markedly by agents that cause hepatonecrosis.
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PMID:Ornithine decarboxylase, serum isocitrate dehydrogenase and clinical chemistry changes during thioacetamide-induced hepatotoxicity in a calf. 734 23

The effect of carrot extract on carbon tetrachloride (CCl4)-induced acute liver damage was evaluated. The increased serum enzyme levels (viz., glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, sorbitol and glutamate dehydrogenase) by CCl4-induction were significantly lowered due to pretreatment with the extract. The extract also decreased the elevated serum bilirubin and urea content due to CCl4 administration. Increased activities of hepatic 5'-nucleotidase, acid phosphatase, acid ribonuclease and decreased levels of succinic dehydrogenase, glucose-6-phosphatase and cytochrome P-450 produced by CCl4 were reversed by the extract in a dose-responsive way. Results of this study revealed that carrot could afford a significant protective action in the alleviation of CCl4-induced hepatocellular injury.
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PMID:Hepatoprotective activity of carrot (Daucus carota L.) against carbon tetrachloride intoxication in mouse liver. 750 Jun 38

The effects of subclinical fasciolosis at various stages of its development on bile flow and bile acid secretion and on the hepatobiliary transport of bilirubin were investigated in experimentally infected sheep. Bile flow was significantly reduced by weeks 6-14 postinfection. This was accompanied by a decrease in bile acid secretion by weeks 6-8. Serum AST and GLDH activities and serum bile acid concentration were significantly elevated from weeks 6 to 14. Total serum bilirubin was maximally increased at 6 weeks postinfection and remained elevated at weeks 8 and 14. Increases corresponded to both unconjugated and conjugated fractions, although the conjugated/total bilirubin ratio was enhanced in all infected animals. Biliary bilirubin secretion declined from weeks 6 to 14. No alteration was detected in either uridine diphosphate (UDP)-glucuronosyltransferase activity, cytochrome P-450 concentration, or hematological markers of hemolysis. This study shows that the migration of immature flukes in the course of ovine fasciolosis causes a cholestatic phenomenon responsible for changes in serum and biliary bilirubin levels.
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PMID:The effects of subclinical fasciolosis on hepatic secretory function in sheep. 773 19


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