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 toxicity of cadmium was examined in rats fed diets containing either tissue-incorporated cadmium or cadmium salt for 4 wk. The test diets contained 30 mg cadmium/kg either as cadmium chloride, or as cadmium incorporated in pigs' livers; the control group was fed a diet containing liver from a pig not treated with cadmium. Over 90% of the cadmium present in the pigs' livers was bound to metallothionein. Analysis of the diet and determination of the food consumption revealed that both cadmium-fed groups were exposed to similar dietary cadmium levels. There was no adverse effect on general health or survival. Feeding cadmium resulted in growth retardation and slightly decreased water intake. Moreover, both cadmium-treated groups showed clear signs of anaemia and increased plasma aspartate and alanine aminotransferase activities. For the group fed cadmium chloride, all of these effects were more pronounced than for the group fed cadmium incorporated in liver. Microscopic examination of the liver and kidneys, however, did not reveal any lesion that could be attributed to the cadmium treatment. After exposure to cadmium the spleen showed decreased extramedullary haematopoiesis, an effect that was also more pronounced after feeding of the cadmium chloride than after feeding liver-incorporated cadmium. The differences in the extent of the toxic effects between the inorganic and the tissue-incorporated cadmium were accompanied by differences in the cadmium concentrations in liver and kidneys: the feeding of cadmium incorporated in pigs' livers resulted in about half the accumulation of cadmium in the rats' livers that took place after intake of a diet containing cadmium chloride. In contrast a much less marked difference in cadmium accumulation was observed in the kidneys. Since humans are usually exposed to tissue-incorporated cadmium these findings deserve further investigation, with special attention to the observed difference in tissue accumulation.
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PMID:Comparison of the toxicity of inorganic and liver-incorporated cadmium: a 4-wk feeding study in rats. 221 May 16

Effect of S-adenosyl-L-methionine disulfate tosylate salt (SAMe-ST) and L-methionine (L-Met) on primary cultured rat hepatocytes were studied. In cultured hepatocytes treated with CCl4, SAMe-ST and L-Met suppressed the decrease in urea-nitrogen secretion as well as the leakages of GOT and GPT. The membrane-protective action of these two compounds was verified by the histological data. Failure of SAMe-ST to counteract CCl4-induced reduction of radioactive leucine incorporation into the trichloroacetic acid-insoluble materials in hepatocytes indicates that the observed effects of SAMe-ST or L-Met do not involve acceleration of protein synthesis. The present results indicate that SAMe-ST remarkably protects hepatocytes from CCl4-induced hepatotoxicity, probably by either changing the structure or compositions of membrane phospholipids or by modifying the interaction of CCl4 with the intracellular drug-metabolizing enzyme systems.
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PMID:Protective effect of S-adenosyl-L-methionine against CCl4-induced hepatotoxicity in cultured hepatocytes. 231 31

Primary human hepatocytes were used to study bile salt hepatotoxicity and the hepatoprotective potential of ursodeoxycholate in vitro. Hepatocytes were obtained by collagenase perfusion of healthy human liver tissue and were treated with glycochenodeoxycholate for 24 hr 1 day after plating. Clear signs of cytotoxicity were observed at concentrations of about 100 mumol/L glycochenodeoxycholate. Toxicity was determined by release of alkaline phosphatase, gamma-glutamyl transferase, AST, ALT or lactate dehydrogenase into the culture medium, by measuring DNA synthesis of the cultured liver cells and by testing the viability of the hepatocytes using trypan-blue dye exclusion. Addition of ursodeoxycholate, which by itself proved to be of little toxicity, significantly reduced the hepatotoxic effects of glycochenodeoxycholate: 72% +/- 6% of the cells survived treatment with 500 mumol/L glycochenodeoxycholate alone, but addition of 100 mumol/L ursodeoxycholate increased the survival rate to 87% +/- 4% (p less than 0.05). Moreover, all enzymes tested were secreted at a significantly lower level when ursodeoxycholate was present. Similarly, the cellular DNA synthesis was maintained at significantly higher levels as a result of ursodeoxycholate treatment. We conclude that (a) primary human hepatocytes are a suitable model for studying hepatotoxicity of bile salts in vitro, (b) ursodeoxycholate reduces hepatotoxicity of other bile salts and (c) ursodeoxycholate can act hepatoprotectively by itself (i.e., alteration of the metabolism of other bile salts is not necessarily required).
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PMID:Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes. 240 54

Bacteriological, pharmacokinetic and clinical studies on cefpodoxime proxetil (CPDX-PR, CS-807), a new oral cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows. 1. Antibacterial activities of R-3746 (Na-salt of cefpodoxime (CPDX] against clinically isolated strains of Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Enterococcus faecalis, Branhamella catarrhalis, Escherichia coli, Proteus mirabilis and Haemophilus influenzae were compared with those of cefaclor, cephalexin and cefadroxil. R-3746 is superior to other antibiotics against S. pneumoniae, S. pyogenes, B. catarrhalis and Gram-negative rods. 2. Serum concentrations of CPDX after administration of CPDX-PR at doses of 3 mg/kg (fasting), 6 mg/kg (non-fasting) and 6 mg/kg (fasting) were determined. Mean AUC (area under curve)'s of CPDX obtained were 9.60, 31.35 and 17.89 micrograms.hr/ml, respectively for the 3 dosages. The mean half-lives of CPDX were 3.35, 1.88 and 1.76 hours, respectively. The mean urinary recovery rate within 8 hours after administration of CPDX-PR at a dose of 3 mg/kg (fasting) was 39.2%. 3. CPDX-PR was administered to 37 pediatric patients with various bacterial infections (pyelonephritis 9, cystitis 4, pneumonia 7, acute bronchitis 3, otitis media 2, tonsillitis 10, subcutaneous abscess 1 and purulent lymphadenitis 1). The overall clinical efficacy rate was 91.9% and the overall bacteriological eradication rate was also 91.9%. 4. No adverse reactions were observed. Abnormal laboratory findings were moderate, eosinophilia in 2 and slight elevation of GOT and GPT in 1. The taste and the odor of the CPDX-PR preparation was sufficiently tolerable. From the above results we have concluded that CPDX-PR is a useful oral antibiotic in the treatment of bacterial infections in children.
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PMID:[Bacteriological, pharmacokinetic and clinical studies on cefpodoxime proxetil in the pediatric field]. 256 89

The effect of therapeutic doses of cyclosporine A (CyA) on bile flow and bile salt output was studied in the rat. Thirty male Sprague-Dawley rats (250 to 380 g) were injected intraperitoneally with CyA (n = 15) or vehicle (n = 15) at the dose of 10 mg.kg-1 for 3 weeks. The effect of CyA on basal and taurocholate-induced bile flow, on basal bile salt output and bile salt output under taurocholate infusion, and the effect of chronic administration of CyA on bile salt-independent bile flow was evaluated. Administration of CyA was associated with a decrease in basal bile flow (5.6 +/- 0.7 vs 6.7 +/- 0.7 microliters.min-1.100 g-1; p less than 0.001) and bile flow under taurocholate infusion (8.0 +/- 0.8 vs 10.9 +/- 1.1 microliters.min-1.100 g-1; p less than 0.001). Basal bile salt output (133.9 +/- 48.2 vs 173.8 +/- 53.6 nmol.min-1.100 g-1; p less than 0.003) and bile salt output under the infusion of taurocholate were significantly lower in cyclosporine-treated rats than in controls (443.3 +/- 48.2 vs 617.2 +/- 172.7 nmol.min-1.100 g-1; p less than 0.001). There was no significant difference in bile salt-independent bile flow between the 2 groups. There was no modification of seric alanine aminotransferase activity or hepatic histology. This study confirms that chronic administration of CyA at therapeutic doses can induce cholestasis. Cholestasis is related mainly to a decrease in bile salt secretion and bile salt-dependent flow.
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PMID:[Effect of chronic administration of cyclosporin A on choleresis in rats]. 259 85

This paper describes in vitro studies on the effects of environmental pollutants (SO2/NOx) in biological systems. Basic physical, chemical and biochemical parameters were analyzed to establish the rate of SO2/NOx absorption by the culture medium. It was shown that the pH remains constant for 24 h of exposure to gas concentrations up to 50 p.p.m. The concentration of ions resulting from absorption of each pollutant in the liquid phase is dependent on their concentration in the gas phase and on exposure time. Short exposure times and high gas dosages resulted in similar doses in the medium as long exposure periods and low gas dosages. The activities of a human serum standard (alkaline phosphatase, ALP; aspartate amino transferase, AST; alanine amino transferase, ALT; gamma-glutamyltransferase, gamma-GT; lactate dehydrogenase, LDH) were determined after gaseous exposure to SO2 and NOx. The results revealed a distinct decrease in the activity of LDH after 1, 3 and 5 h exposure to 200 p.p.m. SO2. The effects of the pollutants were assayed in vitro using fetal hamster lung cells (FHLC), rat hepatocytes and the cell line CO60. For the determination of toxic effects, it was shown that the plating efficiency was a more sensitive parameter than the assay for trypan blue exclusion. Toxicity indicated as an increase of LDH leakage was not observed from FHLC in culture. Instead, a decrease of LDH was found following SO2 exposition. This decrease was similar to that observed for the human serum standard. The induction of DNA single-strand breaks was determined as a measure of genotoxic effects. SO2 application decreased the rate of DNA single-strand breaks induced by N-nitroso-acetoxymethyl-methylamine in both FHLC and in rat hepatocytes. SO2 or NOx treatment of CO60 cells for 1 h did not result in the induction of DNA amplification. HSO3- added directly to the medium as the sodium salt, however, distinctly induced the amplification of SV40 DNA. The amplification rates induced by benzo[a]pyrene or dimethylbenzanthracene were neither influenced by SO2, NOx nor HSO3-. An additive effect of HSO3- with either benzo[a]pyrene or dimethylbenzanthracene for this biological parameter was therefore not observed.
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PMID:Effects of SO2 or NOx on toxic and genotoxic properties of chemical carcinogens. I. In vitro studies. 283 97

A 32-year-old male (Mr. A.), monitored during an 8-d heat acclimation (HA) investigation, unexpectedly exhibited heat intolerance and heat exhaustion. Thirteen other males completed HA without indications of either heat intolerance or heat exhaustion. Because Mr. A. responded normally to HA on days 1-4, the intervention of an unknown host factor on days 5-8 was suggested. Mr. A.'s heat exhaustion episode (day 8) was apparently forewarned by loss of body weight and increased delta HR, delta Tsk (days 5-8) and delta Tre (days 7-8) during daily 90-min trials. His symptoms indicated classical salt depletion heat exhaustion, but the calculated salt deficit (less than 0.1 g NaCl.kg-1 body weight) was mild. Post-heat exhaustion serum enzyme levels were either normal (ALT, AST) or acutely elevated (CPK). Blood beta-endorphin and cortisol levels were six times and two times greater than control values, respectively. This case report is unique because clinical/physiological measurements and blood analyses were performed before, during, and after heat intolerance and heat exhaustion.
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PMID:Heat intolerance, heat exhaustion monitored: a case report. 335 82

It was recently suggested that the apparent biliary transport maximum (Tm, secretory maximum) for bile salts is primarily determined by their degree of cytotoxicity (the cytotoxicity hypothesis), based on experiments on male rats [Hardison, W. G., D. E. Hatoff, K. Miyai, and R. G. Weiner. Am. J. Physiol. 241 (Gastrointest. Liver Physiol. 4): G337-G343, 1981]. To confirm this hypothesis, we determined the Tm of three different bile salts, taurocholate (TC), taurochenodeoxycholate (TCDC), and tauroursodeoxycholate (TUDC) in female rats and hamsters. The order of Tm values in female rats was the same as that reported for male rats (TUDC greater than TC greater than TCDC), whereas in female hamsters it was TC greater than TCDC greater than TUDC. On the other hand, in hamsters, the order of cytotoxicity, evaluated in vivo by the biliary excretion of hepatocyte enzymes such as lactate dehydrogenase and alkaline-phosphatase and an increase in plasma lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase levels under a fixed rate infusion (0.6 and 1.2 mumol X min-1 X 100 g body wt-1) of bile salts, was inverse to the order of Tm values (TCDC greater than TC greater than TUDC) in rats, but in hamsters, too, TCDC was most cytotoxic. The order of Tm value in hamsters thus does not correspond to the order of cytotoxicity of these bile salts, suggesting that the cytotoxicity of bile salts may not be the sole determinant of bile salt Tm.
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PMID:Differing transport maxima values for taurine-conjugated bile salts in rats and hamsters. 378 51

Concentrations of conjugated cholate, chenodeoxycholate, direct bilirubin, and alanine aminotransferase (ALT, EC 2.6.1.2) were measured in plasma of 122 low-birthweight infants receiving parenteral nutrition. Eighteen (15%) of them developed hepatic dysfunction. We observed two distinct biochemical patterns in these infants. In the Type A pattern (12 infants), concentrations of direct-reading bilirubin and bile salts increased with no change in ALT activity. In the Type B pattern (six infants), increases in the concentrations of bile salt and direct bilirubin were followed by increases in ALT activity. Hepatic dysfunction persisted significantly longer in infants who developed the Type B pattern. The two patterns did not differ significantly in the times at which values for bile salts or direct bilirubin in plasma became abnormal or became normal at resolution, nor did maximal concentrations of bile salts in plasma differ significantly. Maximal concentrations of direct bilirubin were higher in the Type B infants. We conclude that, in such infants, measurement of bile-salt concentrations in plasma offers no advantages for detecting hepatic dysfunction over the more conventional measurement of direct bilirubin in plasma.
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PMID:Measuring bile-salt concentrations lacks clinical value for detecting hepatic dysfunction in infants receiving parenteral nutrition. 392 41

We examined 17 lots of 2-oxoglutarate (seven acid forms, three K salt forms, and seven Na salt forms), obtained from eight commercial suppliers, for suitability for measuring aspartate aminotransferase (EC 2.6.1.1) and alanine aminotransferase (EC 2.6.1.2) in human serum. Measurements of the catalytic activity concentrations of these two aminotransferases with each of these 17 preparations were not sufficiently sensitive to distinguish good from poor-quality material. Thus, we ranked these lots for purity, by specific analysis with glutamate dehydrogenase and by liquid chromatography, and determined the water content, acid content, and spectral characteristics of each. On the basis of a 2-oxoglutarate assay value by glutamate dehydrogenase of 98% or greater, we considered seven of the preparations acceptable and 10 unacceptable. The molar absorptivities (L X mol-1 X cm-1, mean +/- SD) of the seven acceptable lots in 1 mol/L HCl were: epsilon 325 nm = 9.12 +/- 0.02 (CV = 0.2%), epsilon 279 nm = 2.63 +/- 0.23 (CV = 9.9%), and epsilon 245 nm = 37.9 +/- 4.1 (CV = 10.9%). Use of these spectrophotometric limits alone unambiguously distinguished the inferior lots of 2-oxoglutarate. We urge the inclusion of detailed spectrophotometric specifications for 2-oxoglutarate in Reference Methods for aminotransferase measurements.
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PMID:Comparisons of 17 lots of 2-oxoglutarate, and specifications for use of this substrate in reference methods. 399 57


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