Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of GOT, GPT, APh, liver APh, gamma GTP, AAP and serum cholinesterase were determined in 80 patients with chronic liver diseases, diagnosed clinically, laparoscopically and by liver biopsy. Out of the patients with liver cirrhosis (51), those with portal cirrhosis (40) have a considerably higher activity of gamma GTP, intestinal APh than the patients with postecrotic cirrhosis (11). Cholinesterase activity is markedly lower in patients with cirrhosis and ascites than in the patients without ascites. With the histological data about the activity gamma GTP and GOT are considerably higher without activity. Examinations were carried out also upon patients with chronic aggressive hepatitis (4), chronic persisting hepatitis (9), liver cancer (12) and liver steatosis (4). The data revealed that the majority of the enzymes are with a higher sensitivity (especially gamma GTP, GOT, liver APh, cholinesterase) but with more restricted diagnostic and differential-diagnostic potentialities in view of the great dispersion of the enzyme activities with the separate liver diseases.
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PMID:[Comparative laparoscopic, bioptic and clinical enzymological studies in liver cirrhosis and other chronic liver diseases]. 14 93

Of a greater number of biochemical tests in hepatobiliary diseases by means of methematico-statistical methods (calculation of specificity and sensitiveness, variance analysis, discrimination analysis with following discrimination experiments) the parameters should be established which in a step programme with multivariate observation and non-discriminated approach give the best possible information. The recognition of patients with liver diseases (preliminary diagnostics) is at nearly 94% possible with a scale comprising GOT, AAP, some relevant clinical data (touch findings, jaundice, hepatic skin signs) and the hepatitis B-antigen. In non-discriminated approach according to our findings the following scale should not be trangressed: GPT, GOT (compare preliminary diagnostics), LAP, AP, AAP (compare preliminary diagnostics), cholesterol, TTT, bilirubin, beta-GC. As to aimed questionings the bromsulphalein test belongs to the enlarged basic scale.
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PMID:[Laboratory diagnosis of liver and biliary tract disease]. 85 Oct 13

In the present paper is reported on the behavior of different serochemical parameters in heterologous perfusion of the liver of pigs. The perfusion of the animal livers was carried out with preserved human blood in 11 recirculation experiments (closed machine circulations). In addition to this an empty circulation with human blood without attachment to an animal liver was carried out, whereby otherwise the arrangement of the experiment was the same, in order to take into consideration the effects of the blood traumatisation in the interpretation of the results. The enzymes GOT and LAP proved as sensible indicators of the lesion of the liver cells occurring in the perfusion of the liver of the pigs. The behavior of the mitochondrial GDH as well as of the lysosomal enzymes SP and BETA-GC which scarcely increased during the recirculations in the perfusate blood, however, allows the conclusion that there did not appear a severe lesion of the liver cells (necrobiosis) during several hours of perfusion. A cholestasis did not develop during the perfusions, when one takes as basis the behavior of the enzymes AP, GGTP and AAP indicating cholestasis. Compared with GOT the enzyme GPT showed by far less elevations in the perfusate blood so that with increasing duration of the perfusion the De-Ritis-quotient significantly increased. Increased LDH-activities above all revealed the increasing during perfusion haemolysis and less reliably a lesion of the liver of the pig. The increase of ADA in the perfusate blood proved as nearly exclusively conditioned by haemolysis. Total protein, albumins, immunoglobulins, cholinesterase and thymol turbidity test remained unchanged in the course of the perfusions.
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PMID:[Studies on the functional ability of swine liver perfused with human blood in machine recirculation attempt. 2. Behavior of serochemical parameters]. 96 Aug 62

Excretion of urinary lactate dehydrogenase (LDH, EC 1.1.1.27), gamma-glutamyltransferase (gamma-GT, EC 2.3.2.2), alkaline phosphatase (ALP, EC 3.1.3.1), alanine aminopeptidase (AAP, EC 3.4.11.-), alanine aminotransferase (GPT, EC 2.6.1.2) and N-acetyl-beta-D-glucosaminidase (NAG, EC 3.2.1.30) was studied following a single i.v. application of 1 mg mercuric chloride/kg body weight or a radio contrast medium (SH H 340 AB) at a dose of 7.5 g iodine/kg body weight in rats. Measurements of urinary enzymes and serum urea nitrogen and creatinine were carried out on the second, third, fourth and ninth days after treatment. Histological examinations of kidneys were performed on day 9. A drastic increase in urinary LDH and moderate increase in gamma-GT, ALP and AAP and a very slight increase in GPT was observed in the first 18-h urine samples after mercuric chloride. This increase in enzymuria was associated with a drastic increase in serum urea nitrogen and creatinine, with a maximum on day 4. The radio contrast medium-treated animals showed a similar but less pronounced pattern of urinary enzymes excretion and only a slight increase of serum urea nitrogen on day 2. A good correlation was found between histological findings and enzymuria as well as serum urea nitrogen and creatinine. Thus, determination of only some urinary enzymes (LDH and gamma-GT) is valuable in predicting early nephrotoxicity and sufficient for the diagnosis of proximal tubule damage in rats.
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PMID:Value of enzyme determinations in urine for the diagnosis of nephrotoxicity in rats. 287 61

In the diagnosis of chronic (as opposed to acute) liver diseases, combinations of indicators are needed to improve specificity. Alanine aminopeptidase (AAP; microsomal aminopeptidase, EC 3.4.11.2) activity in serum reportedly is a very sensitive indicator of intrahepatic cholestasis and biliary obstruction; it is also particularly useful in diagnosing chronic liver disease when combined with an indicator of hepatocyte damage such as aspartate aminotransferase or alanine aminotransferase. We optimized the assay of AAP in serum, automated the assay by using a centrifugal analyzer, then used this automated assay to determine activity in 202 individuals, ages one to 73 years. The preliminary results were analyzed in terms of the effects of age, sex, smoking, and alcohol consumption on AAP activity in serum. Striking sex-related differences were observed: AAP activity in males declined 2.5 times more rapidly with age than did that in females; indeed, activity in adult females remained essentially constant. Moreover, AAP values were higher in men who smoked than in those who did not, the difference being of borderline significance by analysis of covariance (p = 0.0865) but significant by partial correlations (p = 0.02). No similar differences were seen for women smokers and non-smokers. When the effects of other variables were held constant, alcohol consumption alone did not significantly correlate with AAP activity in men or women.
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PMID:Alanine aminopeptidase in serum: automated optimized assay, and effects of age, sex, smoking, and alcohol consumption in a selected population. 288 Jun 80

Experiments were undertaken to examine the ability of selenium to protect against acetaminophen-induced hepatotoxicity and to examine possible mechanisms for this protective effect. Pretreatment of male, Sprague-Dawley rats with sodium selenite (12.5 mumol Se/kg, ip) 24 hr prior to acetaminophen administration produced a significant protection against the hepatotoxic effects of acetaminophen as assessed by a decrease in the plasma appearance of alanine aminotransferase and aspartate aminotransferase activities following acetaminophen. This was accompanied by an increase in the hepatic glutathione levels in selenium-treated animals and an inhibition in the decrease in hepatic glutathione content observed in animals receiving hepatotoxic doses of acetaminophen. Selenium pretreatment decreased the in vivo covalent binding of acetaminophen metabolites to hepatic protein, but did not alter hepatic microsomal cytochrome P-450 content or NADPH cytochrome c reductase activity, suggesting that selenium does not significantly alter the metabolism of acetaminophen to reactive electrophilic metabolites by the cytochrome P-450-dependent mixed-function oxidase enzyme system. Selenium produced an increase in the activity of gamma-glutamylcysteine synthetase which may account for the increased glutathione availability in selenium-treated animals and increased the activities of glutathione S-transferase and glucose-6-phosphate dehydrogenase. Examination of the urinary metabolite profile in selenium-treated animals revealed that the urinary excretion of acetaminophen and its metabolites was significantly increased over a 72-hr period. The increase occurred in the AAP-glucuronide metabolite while parent AAP and AAP-sulfate were actually decreased in selenium-treated rats. No change in recovery was observed in the AAP-glutathione or AAP-mercapturate urinary metabolites. While the glutathione conjugating system is enhanced by selenium treatment, amelioration of acetaminophen toxicity is most likely the result of enhanced glucuronidation which effectively diverts the amount of acetaminophen to be converted by the cytochrome P-450 system to the toxic metabolite.
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PMID:Protective effects of selenium on acetaminophen-induced hepatotoxicity in the rat. 290 Nov 47

In the present work, the hepatoprotection of EGF was studied on an acetaminophen induced acute injury model of serum-free primary cultured mouse hepatocytes. The results were as follows: (1) When serum-free cultured mouse hepatocytes were exposed to acetaminophen (AAP 20 mmol/L) for 12-14 h, the activity of GPT and GOT were increased to a stable level, serving as a good hepatocyte injury model. (2) EGF of different doses (50, 100, 500, and 1000 ng/ml) added to the medium prior to acetaminophen could reduce hepatocyte injury in a dose-dependent manner. (3) Taking 3H-TdR incorporation as an index, it was observed that acetaminophen could reduce the DNA synthesis of hepatocytes, and pretreatment with EGF could reverse this effect, but, stimulation of DNA synthesis by EGF was not correlated with its hepatoprotection. Thus the reversion of the reduced DNA synthesis in EGF-pretreated hepatocytes is interpreted as the result rather than the cause of cytoprotection of the factor. (4) The hepatoprotection might be produced through affecting on the glutathione metabolism of hepatocytes.
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PMID:[Cytoprotective effect of epidermal growth factor on acetaminophen induced acute injury of hepatocytes]. 808 73

To investigate the importance of the cadmium (Cd) exposure condition in the evaluation of toxic effect on renal function and bone metabolism, six groups of Male Wistar rats were given Cd at respective daily doses of 2, 5, 10, 20, 30 and 60 mgCd/kg (as CdCl2) via a gastric tube for 6 consecutive days a week for 60 weeks. In the groups given a low Cd dose (2, 5 and 10 mgCd/kg), relatively more Cd accumulated in the kidney without liver damage than in the liver. In the high Cd dose groups (20, 30 and 60 mgCd/kg), on the other hand, more Cd accumulated in the liver than in the kidney. The daily intake of Cd dose from the intestinal tract in each experimental group was deduced to be about 0.36%-0.54% of the cumulative dose of oral Cd administration. The daily intake of Cd into the body was estimated as 7, 22, 40, 100, 120, 260 microgCd/kg/day in the experimental groups of 2, 5, 10, 20, 30 and 60 mgCd/kg/day, respectively. Increase of plasma enzyme activity (GOT, GPT) and of urinary enzyme excretion (NAG, AAP, GST), reflecting hepatic damage and renal dysfunction, was found in the high Cd dose groups (30 and 60 mgCd/kg) from the 5th week. Non-CdMT concentration in the kidney was also significantly high in the high Cd dose groups. In the low Cd dose groups (2 and 5 mgCd/kg), although the renal Cd concentration was higher than that of the high Cd dose groups, prominent renal dysfunction and hepatic damage were not observed. Regeneration, vacuolization, and eosinophilic bodies in proximal tubular tissue were mainly observed in the groups subjected to 20, 30 and 60 mgCd/kg administration. Very slight regeneration was also observed in the renal proximal tubular tissue at the 30th week for the 5 mgCd/kg and 10 mgCd/kg groups, and at the 60th week for the 2 mgCd/kg group. Remarkable decrease of bone mineral density at the midpoint of the femur was found in the high Cd dose groups. Also, the decrease in bone mineral density was observed before or after the manifestation of the renal dysfunction, depending on the dose and the duration of Cd administration. Urinary excretion of Pyr, DPyr, and Ca increased and plasma BGP decreased in the higher Cd dose groups. Osteoid volume in the femur tissue was not increased significantly by Cd exposure. Based on these results, it was suggested that Cd exposure caused osteoporotic change. The results of the present study suggested that the toxic effect of Cd on renal function and that on bone metabolism were caused at different times and that renal Cd concentration after long-term oral Cd administration depended on the dose and the duration of Cd exposure.
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PMID:Relationship between renal dysfunction and bone metabolism disorder in male rats after long-term oral quantitative cadmium administration. 1106 77

Mitochondrial oxidant stress and peroxynitrite formation have been implicated in the pathophysiology of acetaminophen-induced (AAP-induced) liver injury. Therefore, we tested the hypothesis that lipid peroxidation (LPO) might be involved in the injury mechanism. Male C3Heb/FeJ mice fed a diet high in vitamin E (1 g d-alpha-tocopheryl acetate/kg diet) for 1 week had 6.7-fold higher hepatic tocopherol levels than animals on the control diet (8.2 +/- 0.1 nmol/g liver). Treatment of fasted mice with 300 mg/kg AAP caused centrilobular necrosis with high plasma alanine aminotransferase (ALT) activities at 6 h (3280 +/- 570 U/l) but no evidence of LPO (hepatic malondialdehyde, 4-hydroxynonenal). Animals on the vitamin E diet had similar injury and LPO as mice on the control diet. To verify a potential effect of the vitamin E diet on drug-induced liver injury, animals were pretreated with a combination of phorone, FeSO4, and allyl alcohol. We observed, 2 h after allyl alcohol, massive LPO and liver cell injury in the livers of animals on the control diet, as indicated by a 32-fold increase in malondialdehyde levels, extensive staining for 4-hydroxynonenal, and ALT activities of 2310 +/- 340 U/l. Animals on the vitamin E diet had 40% lower hepatic malondialdehyde levels and 85% lower ALT values. Similar results were obtained when animals were treated for 3 days with alpha- or gamma-tocopherol (0.19 mmol/kg, ip). Both treatments reduced LPO and injury after allyl alcohol but had no effect on AAP hepatotoxicity. Thus, despite the previously shown mitochondrial oxidant stress and peroxynitrite formation, LPO does not appear to be a critical event in AAP-induced hepatotoxicity.
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PMID:Role of lipid peroxidation as a mechanism of liver injury after acetaminophen overdose in mice. 1294 90

Seaweeds contribute to the maintenance of health through their nutritional and medicinal properties. The effects of PYP, a 14 kDa protein isolated from a hot-water extract of the marine alga Porphyra yezoensis, on AAP-induced liver injury in rats was evaluated. AAP induced acute liver injury and AAP-induced hepatotoxicity is the leading cause of liver failure. In this study, male Sprague-Dawley rats were assigned to one of three treatment groups: control, AAP, or AAP + PYP. Compared with the control group, liver tissue from the AAP group showed increased levels of caspase-3 activity and DNA fragmentation, decreased levels of GSH and increased serum GOT/GPT levels. In contrast, treatment with AAP + PYP produced levels of caspase-3 activity, DNA fragmentation, GSH and GOT/GPT that matched the values seen in the control group. It is concluded that PYP may prevent AAP-induced liver injury.
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PMID:Chemoprotective effects of a protein from the red algae Porphyra yezoensis on acetaminophen-induced liver injury in rats. 1872 49


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