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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postmortem biochemical indices may provide a useful adjunct to morphological studies in the identification of antemortem brain insult. We studied 34 routine medico-legal cases categorising them into one of four diagnostic groups. There were 11 cases of head trauma, 7 of 'hypoxia' (3 hangings and 4 carbon monoxide or drug poisonings), 7 sudden cardiac deaths and 9 miscellaneous cases. Survival time and postmortem interval was known for each case. The degree of cranio-cerebral trauma was graded. Cerebro-spinal fluid (CSF) and vitreous humour were analysed for calcium, glucose, total proteins, aldolase, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyltransferase (GGT), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase BB isoenzyme (CK-BB). CK-BB was also measured in superior vena cava serum. In CSF there was a significant correlation between the severity of cranio-cerebral trauma and levels of aldolase, CK-BB, AST, ALT and total proteins. CSF CK-BB, median units/l (range), for the groupings of head trauma, hypoxia, sudden cardiac death and miscellaneous were respectively 823 (2-3431); 96 (2-187); 4 (2-25); 5 (1-69). Corresponding serum CK-BB levels were 240 (28-322); 390 (26-411); 180 (20-482); 79 (18-530).
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PMID:Efficacy of cerebro-spinal fluid biochemistry in the diagnosis of brain insult. 160 50

The mercapturate S-(2-bromo-2-chloro-1,1-difluoroethyl)-N-acetyl-L-cysteine, which is apparently derived from the halothane degradation product 2-bromo-2-chloro-1,1-difluoroethene, is excreted in urine. S-(2-Bromo-2-chloro-1,1-difluoroethyl)glutathione (BCDFG) and S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine (BCDFC) are putative intermediates in the metabolism of 2-bromo-2-chloro- 1,1-difluoroethene and are analogs of nephrotoxic and cytotoxic S-haloalkyl glutathione and cysteine conjugates. The objective of the research was to study the nephrotoxicity and cytotoxicity of 2-bromo-2-chloro-1,1-difluoroethene-derived S-conjugates. BCDFG and BCDFC were nephrotoxic in Fischer 344 rats and caused diuresis, increases in urine glucose and protein concentrations, in blood urea nitrogen concentrations, in kidney/body weight percentages and in serum glutamate-pyruvate transaminase activities. Both S-conjugates also produced severe morphological changes in the kidneys, especially in the proximal tubules. Morphological changes indicative of hepatotoxicity were seen in some animals given BCDFG and BCDFC. Both BCDFG and BCDFC were cytotoxic to LLC-PK1 cells, as shown by lactate dehydrogenase release into the medium. The cytotoxicity of BCDFG was blocked by the gamma-glutamyltransferase inhibitor acivicin, and the cytotoxicity of both BCDFG and BCDFC was blocked by the cysteine conjugate beta-lyase inhibitor aminooxyacetic acid. Also, S-(2-bromo-2-chloro-1,1-difluoroethyl)-DL-alpha-methylcysteine, which can not be metabolized by beta-lyase, was not toxic to LLC-PK1 cells. These in vivo and in vitro data provide evidence that BCDFG and BCDFC are nephrotoxic and that their toxicity is dependent on renal bioactivation by cysteine conjugate beta-lyase.
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PMID:Nephrotoxicity of the glutathione and cysteine conjugates of 2-bromo-2-chloro-1,1-difluoroethene. 160 87

In the present study, we investigated the toxic response to repeated oral administration of 2-chloroethyl linoleate (2-CEL) in male rats at 250 mg/kg body weight for 2 weeks on alternate days (total 7 doses). Control rats received an equal volume of mineral oil. The five animals from each group were sacrificed on days 1, 7 and 28 following the last dose. No significant changes were observed in body weight, as well as organ-to-body weight ratios due to 2-CEL treatment. The red blood cell counts increased significantly in 2-CEL treated animals at day 28 as compared to the controls. Elevated counts of platelets, monocytes and eosinophils and low counts of basophils and large unstained cells were also observed at some time points in 2-CEL treated rats. Significantly reduced activities of total serum lactate dehydrogenase (LDH), aspartate aminotransferase and alanine aminotransferase were found at most of the time points except for LDH at day 28. Adenosine triphosphatase activity was also significantly reduced in liver mitochondrial fraction at all time points. Histopathological studies showed consistent centrilobular lesions (incidence 4/4) in the liver consisting of hepatocyte vacuolar degeneration and focal necrosis at day 28. A few centrilobular lesions were also observed (incidence 2/4) at day 7, while no changes were observed at day 1. These results indicate that 2-CEL is a hepatotoxin, however, the observed decrease in serum enzyme levels in relation to hepatotoxicity of 2-CEL, needs to be elucidated.
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PMID:Toxic response to repeated oral administration of 2-chloroethyl linoleate in rats. 160 45

Egyptian scorpion venom was collected by electrical stimulation of the telson. Rats were injected with the lyophilized venom in 3 different doses (100, 200 and 400 micrograms/kg). Blood samples were drawn by heart puncture before and 4 h after venom administration. Serum was separated and collected for determination of glucose, blood urea nitrogen (BUN), creatinine, uric acid (UA), total proteins, cholesterol, sodium, potassium, calcium, inorganic phosphorus, alkaline phosphatase, aspartate aminotransferase (AST, GOT), alanine aminotransferase (ALT, GPT), lactate dehydrogenase and creatine phosphokinase (CPK). Serum glucose, creatinine, GOT, GPT and LDH were increased significantly in all treatments. At the same time serum BUN and CPK were elevated significantly with a dose-response relationship. On the other hand, serum total proteins, uric acid, cholesterol, calcium and potassium were significantly decreased 4 h after administration of the 3 doses. These changes in clinical chemistry parameters are most probably related to the toxic effect of the venom on the target organs.
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PMID:Effect of scorpion Leiurus quinquestriatus (H&E) venom on the clinical chemistry parameters of the rat. 160 45

A system consisting of isolated rat hepatocytes immobilized in agarose threads continuously perifused with oxygenated Krebs-Henseleit (KH) solution has been found to maintain cell viability with excellent metabolic activity for more than 6 h. The hepatocytes were monitored by phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy at 4.7 Tesla, by measurement of oxygen consumption and by the leakage of lactate dehydrogenase (LD) and alanine aminotransferase (ALT). The data obtained were comparable to those found for an isolated perfused whole liver in vitro. The effects of allyl alcohol (AA), ethanol, and 4-acetaminophenol (AP) were examined. A solution of 225 microM AA perifused for 90 min caused the disappearance of the beta-phosphate resonance of adenosine triphosphate (ATP) in the 31P-NMR spectra, a 7-fold increase in LD leakage and a 70% reduction in oxygen consumption. Ethanol (1.0 M) perifused for 90 min reduced the beta-ATP signal intensity ratio by 20%, the phosphomonoester (PME) signal by 50% and inorganic phosphate (Pi) by 33% (P less than 0.05). AP (10 mM) caused only mild liver-cell damage. The results demonstrate that perifused immobilized hepatocytes can be used as a liver model to assess the effects of a wide range of chemicals and other xenobiotics by NMR spectroscopy.
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PMID:31P-NMR spectroscopy of perifused rat hepatocytes immobilized in agarose threads: application to chemical-induced hepatotoxicity. 161 Sep 10

A 26-year-old woman who received methimazole treatment for Graves' disease is discussed. Two months following treatment, her serum GOT level rose to 45 K.U, her GPT to 60 K.U, and her lactate dehydrogenase (LDH) to 645 W.U; a hepatic disorder was then suspected. Later, the serum GOT and GPT concentrations decreased to a normal range, but her serum LDH continued to maintain a high level. An LDH isoenzyme analysis showed an abnormally broad LDH. The IgG that was linked to the LDH is suspected to have been the result of her underlying autoimmunity, the methimazole treatment, and the development of her hepatic disorder. Thus, this IgG was thought to be the autoantibody to LDH.
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PMID:Lactate dehydrogenase (LDH)-linked immunoglobulin in a patient with Graves' disease treated with methimazole. 161 Nov 90

We report the development of severe hepatotoxicity in a patient on zidovudine therapy who received 3.3 g of acetaminophen in less than 36 hours. Three days later, the patient's serum aspartate aminotransferase level was 5,724 U/L, alanine aminotransferase was 3,124 U/L, lactate dehydrogenase was 12,675 U/L, alkaline phosphatase was 84 U/L, and total bilirubin was 20 mumol/L. These values substantially improved over the ensuing 4 days. Serologic results for hepatitis B, hepatitis A, and cytomegalovirus were all negative. The pattern and time sequence of transaminase elevation in this patient are consistent with acute acetaminophen hepatotoxicity, especially since zidovudine-induced hepatotoxicity is described as producing cholestasis rather than acute hepatitis. We hypothesize that our patient's susceptibility to acetaminophen-dependent hepatotoxicity may have been augmented by competitive utilization of glucuronidation by other drugs such as zidovudine and/or trimethoprim-sulfamethoxazole with subsequent increased cytochrome P450-dependent metabolism of acetaminophen. Additionally, due to malnutrition and/or to human immunodeficiency virus infection per se, our patient may have had decreased hepatic reserves of glutathione with which to conjugate the toxic acetaminophen product of the P450 system. Although severe acetaminophen-associated hepatotoxicity has not previously been reported in patients receiving zidovudine, we suggest that clinicians be aware of this potential interaction and counsel malnourished patients, especially those with concomitant hepatic disease, to exercise caution when taking both these medications.
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PMID:Severe hepatotoxicity in a patient receiving both acetaminophen and zidovudine. 836 34

Allyl alcohol injury to hepatocytes in the perfused liver is oxygen-dependent. It is not known if this injury involves direct action of allyl alcohol on hepatocytes or requires participation of other cell types (e.g., Kupffer cells) present in the liver. Accordingly, the action of allyl alcohol (100-500 microM) on isolated hepatocytes was studied using cells maintained at either 95 or 21% O2. Allyl alcohol toxicity, as indexed by trypan blue uptake, lactate dehydrogenase release, and ATP content, did not differ in the two groups of cells, suggesting that O2 dependency of allyl alcohol toxicity involves other cell types. Administration of allyl alcohol (30 or 40 mg/kg, ip) to rats caused extensive hepatic necrosis localized primarily to periportal regions. To test the involvement of Kupffer cells in the genesis of this injury, male rats (200-350 g) were treated with gadolinium chloride (GdCl3, 10 mg/kg, iv) which diminishes Kupffer cell function and number. The extent of hepatic damage assessed by light microscopy and serum enzymes, aspartate aminotransferase and alanine aminotransferase, was markedly attenuated by pretreatment of rats with GdCl3 24 hr prior to allyl alcohol injection. Thus, O2-dependent hepatic necrosis caused by allyl alcohol involves the presence of Kupffer cells. Since GdCl3 did not prevent toxicity in the perfused liver, circulating blood elements may also contribute to injury of the liver by allyl alcohol in vivo.
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PMID:Involvement of nonparenchymal cells in oxygen-dependent hepatic injury by allyl alcohol. 163 94

Chloroform hepatotoxicity was investigated in precision-cut liver slices from male Sprague-Dawley rats pretreated with phenobarbital to predispose animals to CHCl3 intoxication. Liver slices were exposed to 0.2, 0.5 and 1.0 mM chloroform for a total of 9 h in a roller culture system. Intracellular K+ loss was found to be concentration- and time-dependent over the duration of the experiment. Histopathological changes were also evident. Glucose 6-phosphate dehydrogenase and beta-glucuronidase were significantly decreased at 3 h relative to controls where a loss of 61% and 36% occurred, respectively. Enzyme levels of alanine aminotransferase and lactate dehydrogenase, both found predominantly in periportal hepatocytes, remained identical to controls over the duration of the experiment. A significant time-dependent depletion of glutathione occurred as early as 3 h following the administration of 0.5 mM chloroform. Mitochondrial viability, measured by the reduction of a specific dye, was significantly lower than controls in treated slices at 6 h following chloroform administration. Precision-cut liver slices appear to be especially useful for the biochemical and histopathological examination of site-specific hepatotoxicants such as CHCl3.
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PMID:The hepatotoxicity of chloroform in precision-cut rat liver slices. 163 1

In order to elucidate the role of mitochondrial dysfunction in paracetamol-induced hepatotoxicity, the effects of paracetamol on the oxygen consumption and ATP content of the isolated perfused rat liver were correlated with parameters of hepatic viability and hepatotoxicity. Paracetamol at 5 g/L reduced the oxygen consumption of the livers by about 80% and hepatic ATP content by 96%. Hepatotoxicity was evident from the nearly complete interruption of bile secretion, a marked release of enzymes [glutamate-pyruvate transaminase (GPT), lactate dehydrogenase (LDH)] in the perfusate, a depletion of hepatic glutathione and an accumulation of calcium in the liver. Paracetamol-induced hepatotoxicity could be prevented completely by using livers from non-fasted rats as well as by addition of fructose to the perfusate of livers from fasted animals. Both treatments resulted in an increased energy supply from anaerobic glycolysis as evidenced by a large release of lactate and pyruvate into the perfusate, but did not inhibit paracetamol-induced decline of oxygen consumption. The decrease in hepatic oxygen consumption depended on the dose of paracetamol and occurred first at a concentration of 0.2 g/L (-10%). LDH and GPT release, on the other hand, was elevated at 2 and 5 g/L and calcium accumulation occurred at 5 g/L paracetamol only. Inhibition of mixed-function oxidases by dithiocarb did not prevent the decrease in oxygen consumption and the resulting hepatic injury induced by paracetamol. The oral administration of the high dose of 5 g/kg paracetamol in vivo to rats exerted strong hepatotoxicity but produced maximal serum levels of 800 mg/L paracetamol only and did not decrease hepatic oxygen consumption as measured in vitro. Our results show that in the isolated perfused rat liver in vitro, only high concentrations of paracetamol can produce "chemical hypoxia" by attacking mitochondria so as to cause hepatic injury. Such high concentrations of paracetamol are not attained in vivo, however. "Chemical hypoxia", thus, seems not to be relevant to the well-known hepatotoxic action of paracetamol.
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PMID:The toxicological relevance of paracetamol-induced inhibition of hepatic respiration and ATP depletion. 163 30


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