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 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

The caffeine test measures the activity of cytochrome p450 (CYP1A2) which is a major enzyme involved in the activation of flutamide. The usefulness of this test in predicting flutamide-induced hepatic injury in patients with prostate cancer was examined. The subjects were: (1). five patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level rose to 100 IU/l or higher following the start of flutamide (moderately injured group); (2). four patients whose AST and ALT levels were higher than normal but less than 100 IU/l (mildly injured group); and (3). two patients whose hepatic function remained normal (normal group). The subjects were each given canned coffee to drink. Urinary caffeine (137X), paraxanthine (17X) and 1, 7-dimethyluric acid (17U) levels were measured 4-5 h later. The metabolite ratio, (17U+17X)/137X, was calculated to serve as an indicator of CYP1A2 activity. The metabolite ratio for the moderately injured group (3.98+/-1.56) and the mildly injured group (5.55+/-1.42) were lower than that for the normal group (9.56). The results suggest that a decrease in CYP1A2 activity is involved in the onset of flutamide-induced hepatic injury, and that the caffeine test seems to provide a useful means of its prediction.
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PMID:Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer. 1249 2

Despite the understanding that some cytochrome P450 isoforms are responsible for activation of paracetamol to the hepatotoxic metabolite, N-acetyl-p-benzoquinineimine (NAPQI), the use of enzyme inhibitors for prevention and/or treatment of paracetamol hepatotoxicity is still not well researched. Here, a mixture of ketoconazole, isoniazid and caffeine (inhibitor solution), known inhibitors of CYP3A, CYP2E1 and CYP1A2, was investigated for prevention of hepatotoxicity after paracetamol over-dose in rats. The appropriate doses of paracetamol (1000 mg/kg/day) and the 'inhibitor solution' (ketoconazole 5 mg/kg, isoniazid 5 mg/kg and caffeine 10 mg/kg; =KIC-5-50), were selected in preliminary experiments. Thereafter, two groups of 15 male Sprague-Dawley rats each were treated with the toxic dose of paracetamol intraperitoneally to induce severe hepatotoxicity. But one of the two groups was treated with the KIC-5-50 intraperitoneally 5 min after administration of paracetamol. Five rats were killed at 24, 48 and 72 hours after paracetamol administration. Plasma concentrations of paracetamol were determined by the polarization fluorescent immunoassay and a piece of liver was sent for histopathology examination. Liver function tests at 48 hours were higher in the 'paracetamol only' treated group than in the 'KIC-5-50 + paracetamol' treated group' (P < 0.05), i.e., median (range) AST 2025 (530-4329) i.u./L, ALT 1174 (662-2395) i.u./L versus AST 194 (81-494) i.u./L, ALT 311 (201-945) i.u./L, respectively. The corresponding plasma concentrations of paracetamol were 0.26 (0.13-1.02) microg/mL for the 'paracetamol only' treated group versus 0.17 (0.07-0.33) microg/ml for the 'KIC-5-50 + paracetamol' treated group. Centrilobular necrosis, the pathogmonomic feature of paracetamol hepatotoxicity, was demonstrated only in the 'paracetamol only' treated group. In conclusion, coadministration of paracetamol with inhibitors of cytochrome P450 prevented the development of paracetamol-induced hepatotoxicity in rats, and this calls for research for enzyme inhibitors that may be of therapeutic value.
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PMID:The role of cytochrome-P450 inhibitors in the prevention of hepatotoxicity after paracetamol overdose in rats. 1502 15

We tested the hypothesis that an acute decrease in muscle TCA cycle intermediates during contraction would compromise aerobic energy delivery. Male Wistar rats were anaesthetized and the gastrocnemius-plantaris-soleus (GPS) muscle complex from one leg was isolated and perfused with a red cell medium containing either saline (Con) or cycloserine (Cyclo; 0.05 mg g-1), an inhibitor of alanine aminotransferase (AAT). After 1 h of perfusion, the GPS muscle was either snap frozen (Con-Rest, n=11; Cyclo-Rest, n=9) or stimulated to contract for 10 min (1 Hz, 0.3 ms, 2 V) with blood flow fixed at 30 ml min-1 (100 g)-1 and then snap frozen (Con-Stim, n=10; Cyclo-Stim, n=10). Maximal AAT activity was>80% lower (P<0.001) in both Cyclo-treated groups (Rest: 0.61+/-0.02; Stim: 0.63+/-0.01 mmol (kg wet wt)-1 min-1; mean+/-s.e.m.) compared to Con (Rest: 3.56+/-0.16; Stim: 3.92+/-0.29). The sum of five measured TCAI (SigmaTCAI) was reduced by 23% in Cyclo-Rest versus Con-Rest but this was not different (P=0.08). However, after 10 min of contraction, the SigmaTCAI was 25% lower (P=0.006) in Cyclo-Stim compared to Con-Stim (1.88+/-0.15 versus 2.48+/-0.11 mmol (kg dry wt)-1). Despite the acute decrease in TCAI after Cyclo treatment, the contraction-induced changes in markers of non-oxidative energy provision (phosphocreatine, ATP and lactate) and the decline in tension after 10 min of stimulation were similar compared to Con. These data do not support the hypothesis that the total muscle concentration of TCAI is causally linked to the rate of mitochondrial respiration during contraction.
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PMID:An acute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle. 1580 96

Coffee consumption is a regular part of daily life throughout the world. Research into the effects of coffee on human health is ongoing, but a recent study suggests that coffee and caffeine consumption can reduce the risk of elevated alanine aminotransferase activity in individuals at high risk for liver disease. This review will analyze the results of that study in light of the current literature.
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PMID:Coffee: good, bad, or just fun? A critical review of coffee's effects on liver enzymes. 1649 69

From a disease-prevention perspective, recent progress in phytochemical and nutraceutical research clearly suggests (benefits outweigh the risk pattern). Although powerful antioxidant properties have been the most acclaimed mechanism of action for these entities, the individual antioxidants studied in clinical trials do not appear to have consistent preventative effects. The actions of the antioxidant nutrients alone do not explain the observed health benefits of diets rich in fruits and vegetables for chronic diseases. Therefore, we proposed that the additive and synergistic effects of phytochemicals in fruits and vegetables are responsible for these potent antioxidant and anticancer activities, and that the benefit of a diet rich in fruits and vegetables is attributed to the complex mixture of phytochemicals present in plants [1]. Surprisingly, however, no studies have attempted to evaluate the combined antitoxic potential of a phytochemical-nutraceutical mixture (PNM) in in vivo models. Therefore, this study, for the first time, was designed to investigate whether pre-exposure to a unique PNM has the ability to impede mechanistic events involved in acetaminophen (APAP)-induced hepatotoxicity. Besides several vitamins and minerals in balanced proportions (approximately US RDA), the PNM used in this investigation contained several well-known phytochemicals such as citrus flavonoids, red wine polyphenols, Garcinia, Gymnema, Ginkgo, Ephedra sinica, Camellia sinensis, Silybum, Guarana, Eluthero, Allium sativum and Ocimum basilicum extracts. To evaluate PNM's antitoxic potential, groups of animals ICR mice, 3 months old) received either a control diet or PNM containing diets (1X and 10X) for 4 weeks. On day-28, animals were divided into two subgroups. Half the animals were administered normal saline and the other half received 400mg/kg ip injections of APAP. All the animals were sacrificed 24h after APAP exposure. Serum and tissue (liver and kidneys) samples were analyzed. APAP alone caused massive liver injury (nearly 495-fold increase in ALT) and oxidative stress (Lipid peroxidation: 268% increase in MDA) coupled with genomic DNA fragmentation (288% increase). Exposure to 1X-PNM for 28 days significantly reduced animal mortality and all the APAP-induced biochemical events (In 1X-PNM + AP: ALT leakage decreased to 54 fold; MDA accumulation decreased to 125%, and DNA fragmentation decreased to 122%), whereas 10X-PNM + APAP slightly escalated both oxidative stress and genomic DNA fragmentation preceding liver injury. Liver homogenates subjected to western blot analysis disclosed the ability of 1X-PNM to counteract APAP-induced decrease in Bcl-xL expression. Histopathological evaluation of stained liver tissue sections indicated anti-apoptogenic and anti-necrogenic reponses coupled with near complete prevention of glycogen depletion by 1X-PNM. Collectively, our investigation suggests that a mixture containing an assortment of phytochemicals/nutraceuticals may serve as a much more powerful blend in preventing drug or chemical-induced organ injuries than a single phytochemical or nutraceutical entity. In addition, ephedra and caffeine containing PNM-exposure in a controlled manner may potentially shield vital target organs from toxicities caused by intentional, unintentional or accidental exposures to structurally and functionally diverse drug and chemical entities.
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PMID:Pre-exposure to a novel nutritional mixture containing a series of phytochemicals prevents acetaminophen-induced programmed and unprogrammed cell deaths by enhancing BCL-XL expression and minimizing oxidative stress in the liver. 1690 8

The aim of the study was examining the effect of fluoride ions and caffeine administration on glucose and urea concentration in blood serum and the activity of protein metabolism enzymes and selected enzymes of the urea cycle in rat liver. The study was carried out using 18 male Sprague-Daowley rats (4.5 mo old). Rats were divided into three groups. Group I received distilled water ad libitum. Group II received 4.9 mg F-/kg body mass/d of sodium fluoride in the water, and group III received sodium fluoride (in the above-mentioned dose) and 3 mg/kg body mass/d of caffeine in the water. After 50 d, the rats were anesthetized with thiopental and fluoride ions, glucose, and urea concentration in blood serum were determined. Also determined were the activities of aspartate aminotransferase, alanine aminotransferase glutamate dehydrogenase, ornithine carbamoylotransferase and arginase in liver homogenates. Liver was taken for pathomorphological examinations. The applied doses of F- (4.9 mg/kg body mass/d) and F- + caffeine (4.9 mg F-/kg body mass/d + 3 mg caffeine/kg body mass/d) resulted in a statistically significant increase of fluoride ion concentration in blood serum, a slight increase of the glucose concentration, and no changes in the concentration of urea in blood serum. This might testify to the absence of kidney lesions for the applied concentrations of F-. No change in the functioning of hepatocytes was observed; however, slight disturbances have been noted in the functioning of the liver, connected with the activation of urea cycle, increase of arginase activity, and accumulation of F- in this organ. There was no observed significant influence of caffeine supplementation on the obtained results.
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PMID:Influence of sodium fluoride and caffeine on the concentration of fluoride ions, glucose, and urea in blood serum and activity of protein metabolism enzymes in rat liver. 1702 82

The effects of caffeinated and non-caffeinated paracetamol administration, with or without vitamins A and E supplementation on the protein and enzyme levels in Wistar albino rats were investigated using caffeinated paracetamol and paracetamol as caffeinated and non-caffeinated paracetamol respectively, and water soluble acetic acid derivatives of vitamins A and E. Serum AST, ALT and ALP levels (u/l) significantly increased [P < 0.05] following paracetamol administration. Caffeination as well as administration of vitamins A and E caused significant decreases[P < 0.05] in AST and ALP levels in all test groups when co-administered with paracetamol and in ALT level except in the caffeinated paracetamol + Vitamin E group in which ALT and ALP level except in the caffeinated paracetamol + vitamin E group in which ALT and ALP levels significantly increased [P < 0.05]. Total serum protein level (g/100ml) significantly increased following caffeination as well as during co-administration of caffeinated paracetamol and Vitamin E; and significantly decreased during co-administration of paracetamol and vitamin A. Paracetamol administration without caffeination or supplementation with vitamin A and E can therefore cause increases in serum liver enzymes that is suggestive of liver necrosis which can be ameliorated to varying degrees by caffeine, vitamin A and E.
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PMID:Serum protein and enzyme levels in rats following administration of antioxidant vitamins during caffeinated and non-caffeinated paracetamol induced hepatotoxicity. 1837 21

Effect of caffeine-coconut products interactions on induction of drug-metabolizing enzyme in Wistar albino rats was studied. Twenty rats were randomly divided into four groups: The control group (1) received via oral route a placebo (4.0 ml of distilled water). Groups 2 to 4 were treated for a 14-day period with 50 mg/kg body weight of caffeine, 50 mg/kg body weight of caffeine and 50 mg/kg body weight of coconut water, and 50 mg/kg body weight of caffeine and 50 mg/kg body weight of coconut milk in 4.0 ml of the vehicle via gastric intubation respectively. One day after the final exposure, the animals were anaesthetized by inhalation of an overdose of chloroform. The blood of each rat was collected by cardiac puncture while the liver of each rat was harvested and processed to examine several biochemical parameters, i.e., total protein and RNA levels, protein/RNA ratios, and activities of alanine and aspartate amino transferase (ALT and AST, respectively). The results showed that while ingestion of coconut milk and coconut water increased the values of protein and protein/RNA ratios, it decreased alanine and aspartate amino transferase (ALT and AST) activities. These effects, in turn, enhanced the induction of the metabolizing enzymes and a resultant faster clearance and elimination of the caffeine from the body, there by reducing the toxic effect on the liver.
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PMID:Effect of caffeine-coconut products interactions on induction of microsomal drug-metabolizing enzymes in Wistar albino rats. 1837 23

In order to investigate the risk-reducing effects of coffee in metabolic syndrome, we performed a study in mice fed a high-fat diet with added coffee and analyzed gene expression in liver and adipose tissues using cDNA microarray. Male C57BL/6J mice were raised for 8 weeks on either a normal diet (N group), a high-fat diet (HF group), or a high-fat diet with 1.1% decaffeinated (HF+DC group) or 1.1% caffeine-containing instant coffee (HF+CC group). The body weights of mice in the HF+DC and HF+CC groups were mostly intermediate between the N and HF groups, even if there were no difference in the amount of diet consumption in each group. Mesenteric fat weight was lower in the HF+DC group than in the HF group (p < 0.05) and tended to become lower in the HF+CC group than in the HF group. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly lower in the HF+DC and HF+CC groups than in the HF group (p < 0.05). Inflammatory cytokine interleukin (IL)-1beta gene expression in liver was up-regulated in the HF group and significantly down-regulated in the HF+DC and HF+CC groups (p < 0.01), while MCP-1 gene expression in white adipose tissue was also significantly suppressed in the HF+DC group (p < 0.01). The induction of these anti-inflammatory responses by coffee consumption may contribute to reducing the risks of metabolic syndrome.
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PMID:Effects of coffee on inflammatory cytokine gene expression in mice fed high-fat diets. 1989 59


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