Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interference by some commonly used analgesic and antirheumatic drugs in the spectrophotometric and colorimetric assays of serum enzymes was examined. None of the investigated methods was significantly influenced by caffeine, phenacetin, ibuprofen or indomethacin. Acetylsalicylic acid affected the continuous assays of creatine kinase and lactate dehydrogenase (with pyruvate as substrate), and the colorimetric assay of alanine aminotransferase. Aminophenazone interfered with the colorimetric method for determination of aspartate aminotransferase and alanine aminotransferase, while phenobarbital interfered only with the continuous method for lactate dehydrogenase (with L-lactate as substrate). Ketoprofen interfered with the colorimetric assays of lactate dehydrogenase and aspartate aminotransferase, while diclofenac affected the continuous assay of aspartate aminotransferase. None of the tested drugs interfered with the continuous methods for the determination of alkaline phosphatase and alpha-hydroxybutyrate dehydrogenase.
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PMID:Effects on analgesic and antirheumatic drugs on the assay of serum enzymes. 649 17

To evaluate its clinical value, the half-life of caffeine (1,3,7-trimethylxanthine) in saliva (SCT) after 3 mg/kg-1 oral caffeine was measured in 53 children with chronic liver disease (mean age, 4.41 years) and 48 control children (mean age, 6.26 years) in five samples over 24 h and compared with parameters of liver function and outcome. Sensitivity was 60.3% and specificity 97% of SCT for diagnosis of chronic liver disease. The correlation of SCT with serum albumin (ALB) was -0.52 (p < 0.001), total bilirubin (SBR) was 0.585 (p < 0.001), prolonged prothrombin time (PT) was 0.387 (p = 0.004), and aspartate aminotransferase (AST) was 0.538 (p = 0.001). The correlation of SCT with a clinical score of liver dysfunction calculated from the presence of features of hepatic decompensation was 0.627 (p < 0.001) and with Malatack's paediatric prognostic score was 0.505 (p < 0.001). Serial SCT and liver function tests were performed on 53 patients on 127 occasions during a mean follow-up of 361 days (range, 4-709). Of this group, 18 were listed for liver transplantation. Predictive values of outcome by analysis of variance expressed as ratio of mean squares were SBR, 34.1 (p < 0.001); log10 SCT, 20.6 (p < 0.001); ALB, 5.2 (p < 0.05); PT, 1.2 (NS). SCT correlated with clinical and biochemical parameters of severity of liver disease, but SBR was a better predictor of listing for liver transplantation in this group of paediatric patients.
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PMID:The prognostic significance of caffeine half-life in saliva in children with chronic liver disease. 771 86

The aim of this study was an experimental assessment of the influence of caffeine on the symptoms of the toxic action of paracentamol in mice as well as a detailed analysis if paracetamol pharmacokinetics in men receiving caffeine at the same time. The toxicologic investigations were performed in 620 Swiss mice. The LD50 and LD100 were determined after an administration of paracetamol intraperitoneally. The effects of two doses of caffeine on the survival time and number of animal deaths were investigated. The degree of hepatic damage was assessed on the basis of biochemical serum criteria, i.e. alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and concentration of bilirubin in serum, as well as on the basis of biochemical investigations of liver homogenates, estimating the concentration of reduced glutathione and P-450 cytochrome in the liver. The anatomicopathologic liver evaluation was also performed, including histological and histopathological examinations (glycogen, lipids). The pharmacological investigations were performed in 9 healthy volunteers in two randomized subgroups with the use of a cross-over method twice at one week intervals. The blood paracetamol level was determined according to the method of Thoma et al. The course of changes of paracetamol plasma levels was described with a one-compartment model for extravascular administration of the drug. The biexponential equation, describing the assumed model, was solved with the method of the smaller squares, using non-linear approximation. (Tab 1-6, Fig. 1-3). The experimental studies demonstrated a decrease in both the acute toxicity and hepatotoxic action of paracetamol administered in combination with caffeine, which was indicated by a significant decrease in aminotransferase and alkaline phosphatase activity and in concentration of bilirubin as well as by an increase in the concentration of P-450 cytochrome and GSH in the liver which decreased after administration of paracetamol alone and also by limitation or lack of hepatic necrosis. The pharmacokinetic calculations in men demonstrated an interaction between paracetamol and caffeine which was indicated by a decrease in plasma paracetamol levels, by a smaller surface under the curve of changes of paracetamol levels indicating faster elimination of the drug after simultaneous administration with caffeine. Therefore, paracetamol preparations with caffeine may be less toxic than paracetamol alone.
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PMID:[Influence of caffeine on toxicity and pharmacokinetics of paracetamol]. 861 54

We investigated the involvement of CYP1A2 in the pharmacokinetics and metabolism of caffeine using mice lacking its expression (CYP1A2 -/-). The half-life of caffeine elimination from blood was seven times longer in the CYP1A2 -/- than wild-type mice. The clearance was concomitantly eight times slower. No parameter that could affect the pharmacokinetics differed between CYP1A2-/-and wild-type mice such as creatinine for kidney function; alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin for liver function; or albumin for protein binding. Other P450s CYP2A, 2B, 2C, 2EI, and 3A were also unchanged in the knockout animals. Caffeine 3-demethylated metabolites thought previously to be characteristic of CYP1A2 (especially 1-methylxanthine and I-methylurate) were also found in the urines of the CYP1A2-/-animals, although at 40% of the level found in wild-type mice. These data indicate that the clearance of caffeine in wild-type mice is primarily determined by CYP1A2.
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PMID:Role of CYP1A2 in caffeine pharmacokinetics and metabolism: studies using mice deficient in CYP1A2. 887 15

We compared the effects of various types of beverages (teas, coffee, and cocoa) on D-galactosamine-induced liver injury by measuring plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in 7-wk-old male Wistar rats. The effects of five fractions extracted with different organic solvents from green tea, different types of dietary fibers, and some short chain fatty acids were also investigated. All of the beverages tested significantly suppressed D-galactosamine-induced enhancement of plasma enzyme activities when powdered beverages were added to the diet (30 g/kg) and fed to rats for 2 wk. Plasma ALT activities were 1155 +/- 82 [micromol/(min.L), control], 289 +/- 61 (green tea), 626 +/- 60 (roasted green tea), 471 +/- 84 (puerh tea), 676 +/- 69 (oolon tea), 423 +/- 76 (black tea), 829 +/- 53 (coffee), and 885 +/- 89 (cocoa). The profile of AST activities was similar. The caffeine-containing fraction from green tea had no significant effect, whereas the other four fractions, including the soluble fiber fraction, significantly suppressed liver injury. In addition to tea fibers, many other types of dietary fiber (hemicellulose, chitin, chitosan, alginate, pectin, guar gum, glucomannan, and inulin, but not cellulose) had liver injury-preventive effects when added to the diet (30 g/kg), suggesting that liver injury-prevention may be one of the general effects of dietary fibers. Of three short-chain fatty acids tested (acetate, propionate, and butyrate), only acetate prevented liver injury when added to the diet (15 g/kg), supporting the possibility that the liver injury-preventive effect of dietary fibers may be mediated at least in part by certain organic acids. These results suggest that several beverages possess preventive effects on certain types of liver injury, such as that induced by D-galactosamine, and that different constituents of high and low molecular weights contribute to the liver injury-preventive effects of green tea.
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PMID:Teas and other beverages suppress D-galactosamine-induced liver injury in rats. 1039 99

Enflurane is a fluorinated volatile anesthetic, mostly eliminated unchanged in exhaled air. About 10% of inhaled enflurane undergoes oxidative metabolism in liver via mixed function oxidase. We examined the influence of ethanol and subchronical exposition (6 hours a day, during five consecutive days) to subanesthetic and anesthetic concentrations of enflurane on liver function in BALB/c mice. Specially designed chamber for inhalatory application of anesthetics was constructed for this study. Animals were divided in six groups of twenty. The ethanol treated group was injected with ethanol intraperitoneally (1 g/kg). Two enflurane treated groups were intraperitoneally injected with 0.9% solution of sodium chloride (10 ml/kg) and one of them exposed to subanesthetic (0.5 Vol%) and the other one to anesthetic (2.75 Vol%) concentrations of enflurane. Following two groups received ethanol (1 g/kg) and each of them inhaled enflurane at previously mentioned doses. The control group was intraperitoneally injected with 0.9 % solution of sodium chloride (10 ml/kg) and did not receive any anesthetic. On the day following the last day of exposure half of the animals from each group were sacrificed for determination of glucose levels, erythrocyte glutathion levels, haematocrit, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), liver protein and glutathion levels, and total cytochrome P-450 (CYP P-450). The other half of animals from each group were injected intraperitoneally with caffeine (20 mg/kg). Caffeine and its metabolites in 8 hour urine were analyzed by high performance liquid chromatography (HPLC) method. Excretion of caffeine and its metabolites was different among the groups. We followed two caffeine metabolic ratios - 1,3-dimethyl uric acid and 3,7-xanthine (1,3-U/3,7-X) and 3,7-dimethyl xanthine + 7-xanthine and 1-xanthine + 1,7-dimethyl uric acid (3,7-X + 7-X/1-X + 1,7-U). The difference in caffeine metabolites ratios suggests that enflurane changes oxidative metabolism in liver via certain subtypes of mixed function oxidase, probably via CYP-4502E1. This effect is more expressed when ethanol and enflurane are applied together. Ethanol is well known inductor of CYP-4502E1 and the registrated enzyme induction could be explained by both influences - of ethanol and enflurane.
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PMID:The influence of anesthetic concentrations of enflurane and ethanol on caffeine metabolism in mice. 1044 95

To clarify the relationship between coffee and fitness, we investigated the effect of coffee on weight gain and total cholesterol as well as production of cytokines and activities of GOT (aspartate aminotransferase; EC 2.6.1.1.) and GPT (alanine aminotransferase; EC 2.6.1.2.) as injected lipopolysaccharides. Forty-eight male Wistar rats were divided into three dietary groups (n=16), which were fed a stock diet (control group), the diet supplemented with freeze-dried coffee of 6.2 g/kg (0.62% coffee group), and the diet supplemented with freeze-dried coffee of 13.6 g/kg (1.36% coffee group). It was confirmed by HPLC analysis that the serum caffeine concentrations in both coffee groups became significantly higher in 140 days after the start of feeding. No significant differences in body weight and serum cholesterol were found between the coffee groups and control group, though the coffee groups tended to be somewhat high at cholesterol level. Activities of serum GOT and GPT increased at 2 h after LPS injection, but in the coffee groups were significantly suppressed (p<0.05). However, the coffee feeding could not suppress the increases of serum cytokine (TNF-alpha and IL-6) levels. These results suggest that coffee may serve as a preventive against liver injury.
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PMID:Coffee and fitness-coffee suppresses lipopolysaccharide-induced liver injury in rats. 1122 4

We conducted a series of in vivo experiments to clarify the hepatoprotective activity of green tea against lipopolysaccharide (LPS) + D-galactosamine (GalN)-induced liver injury and to elucidate the mechanism by which green tea exerts its effect in 7-wk-old male Wistar rats. Liver injury was assessed by plasma alanine aminotransferase and aspartate aminotransferase activities. Green tea extract significantly suppressed LPS + GalN-induced liver injury when added to the diet (30 or 35 g/kg) and fed to rats for 14 d or when force-fed alone (0.4-1.2 g/kg body) 1.5 h before the injection of drugs. Although all five of the fractions extracted from green tea extract with different organic solvents had significant suppressive effects, the caffeine-containing fraction exhibited the strongest effect, suggesting that the protective effect of green tea against LPS + GalN-induced liver injury is attributable mainly to caffeine. Authentic caffeine also significantly suppressed LPS + GalN-induced liver injury when added to the diet (2 g/kg) and fed to rats for 14 d. Dietary green tea suppressed LPS + GalN-induced apoptosis of liver cells, as assessed by DNA fragmentation. However, dietary green tea did not suppress LPS-induced enhancement of plasma concentration of tumor necrosis factor (TNF)-alpha, the cytokine that is thought to play a pivotal role in the pathogenesis of LPS-induced liver injury, although it significantly suppressed plasma concentrations of interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10 and interferon (IFN)-gamma. TNF-alpha + GalN-induced liver injury and apoptosis were also suppressed by dietary green tea. In contrast, dietary caffeine significantly suppressed LPS-induced enhancement not only of plasma IL-1beta, IL-6, IL-10 and IFN-gamma concentrations, but also of TNF-alpha concentration. The results suggest that green tea might suppress LPS + GalN-induced liver injury mainly through the inhibition of TNF-alpha-induced apoptosis of hepatocytes, rather than through the suppression of TNF-alpha production, although the suppressed production of TNF-alpha may be associated with the hepatoprotective effect of caffeine.
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PMID:Green tea suppresses lipopolysaccharide-induced liver injury in d-galactosamine-sensitized rats. 1134 Jan 16

A coffee extract significantly suppressed lipopolysaccharide (LPS)-induced hepatitis in D-galactosamine-sensitized rats, as assessed by the plasma alanine and aspartate aminotransferase activities, when it was added to the diet (30 g/kg) and fed to rats for 14 days. Its effect was as strong as that of a green tea extract. The coffee extract suppressed LPS-induced hepatitis when singly force-fed (1.2 g/kg) 1.5 h prior to the injection of the drugs, whereas a decaffeinated coffee extract had no significant effect. The hepatoprotective effect of caffeine was stronger than that of theobromine. These results indicate that coffee can protect animals from LPS-induced hepatitis, and that the effect of coffee might be mainly due to caffeine.
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PMID:Suppressive effect of coffee on lipopolysaccharide-induced hepatitis in D-galactosamine-sensitized rats. 1157 46

The effects of chronic free access to caffeine (0.01% or 0.05%) in drinking water and subsequent withdrawal on spontaneous motor activity for 24 hours and some related parameters were examined in 8-week-old male and female ICR mice. In the males, the 0.01% group showed little response, but in the 0.05% group the activities in both light- and dark-phases and, consequently, in total increased and peaked on day 5 of treatment. The response gradually decreased on days 15 and 30 and reached the control level after 30 days of caffeine withdrawal. Meanwhile, in the females, the activity was stimulated by both 0.01% and 0.05% of caffeine, at the dark- and light-phases in the former and latter, respectively. The response peaked at 30 days and decreased near to the control level thereafter in both groups. Caffeine affected little the food intake; however, water intakes were higher and lower than the control in the 0.05% and 0.01% male groups, respectively, but the opposite was true in the females. Plasma component levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol and glucose were higher than the control in the males and females treated with 0.05% of caffeine. The caffeine had little effect on the body weight change, organ weights and external appearance throughout the experiment. Thus, the sex- and dose-related differences in the responses to caffeine of spontaneous motor activity and related parameters were proved under physiological conditions.
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PMID:Effects of chronic treatment with caffeine on behaviour and related parameters in male and female mice. 1188 35


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