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)

The aims of the present study were to characterize the subchronic toxicity of chloroform by measuring tissue injury, repair, and distribution of chloroform and to assess the reasons for the development of tolerance to subchronic chloroform toxicity. Male Swiss Webster (SW) mice were given three dose levels of chloroform (150, 225, and 300 mg/kg/day) by gavage in aqueous vehicle for 30 days. Liver and kidney injury were measured by plasma ALT and BUN, respectively, and by histopathology. Tissue regeneration was assessed by (3)H-thymidine incorporation into hepato- and nephro-nuclear DNA and by proliferating cell nuclear antigen staining. In addition, GSH and CYP2E1 in liver and kidney were assessed at selected time points. The levels of chloroform were measured in blood, liver, and kidney during the dosing regimen (1, 7, 14, and 30 days). Kidney injury was evident after 1 day with all three doses and sustained until 7 days followed by complete recovery. Mild to moderate liver injury was observed from 1 to 14 days with all three dose levels followed by gradual decrease. Significantly higher regenerative response was evident in liver and kidney at 7 days, but the response was robust in kidney, preventing progression of injury beyond first week of exposure. While the kidney regeneration reached basal levels by 21 days, moderate liver regeneration with two higher doses sustained through the end of the dosing regimen and 3 days after that. Following repeated exposure for 7, 14, and 30 days, the blood and tissue levels of chloroform were substantially lower with all three dose levels compared to the levels observed with single exposure. Increased exhalation of (14)C-chloroform after repeated exposures explains the decreased chloroform levels in circulation and tissues. These results suggest that toxicokinetics and toxicodynamics (tissue regeneration) contribute to the tolerance observed in SW mice to subchronic chloroform toxicity. Neither bioactivation nor detoxification appears to play a decisive role in the development of this tolerance.
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PMID:Adaptive tolerance in mice upon subchronic exposure to chloroform: Increased exhalation and target tissue regeneration. 1663 Jun 38

Oral administration of alcoholic extracts of Schouwia thebica Webb showed that extracts are safe for human use. The studied extracts are considered safe, since they failed to induce death of mice in doses up to 4000 mg/kg body weight. Hepatoprotective activity was studied for the total alcoholic extracts. The total extract was fractionated in turn with diethyl ether, chloroform, ethyl acetate, and n-butanol, respectively. These extracts were tested for possible hepatoprotective activity. It was found that the ethyl acetate and n-butanol extracts of S. thebica Webb showed hepatoprotective activity. These extracts significantly reduced the increase in activities of ALT, AST, and GGT, and levels of glucose, triglycerides, and cholesterol in serum of CCl(4)-treated rats. The extracts showing activity were found to contain flavonoids; one new compound, chrysoeriol-7-O-xylosoide- (1,2)-arabinofuranoside (2), in addition to another known four compound chrysoeriol (1), quercetin (3), quercetin-7-O-rhamnoside (4), and kaempferol-3-O-beta-D-glucoside (5). The isolated new compound was mainly found to be responsible for this activity when tested on animals in the laboratory. The structures were established by melting point, UV spectroscopy, EI-Mass, Fab-Mass, and 1D and 2D NMR spectroscopic techniques on a 600MHz instrument.
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PMID:Hepatoprotective activity of Schouwia thebica webb. 1679 83

The suspensions of chloroform extract of leaves in 0.3% carboxy methyl cellulose (CMC) was evaluated for hepatoprotective activity in Wistar albino rats by inducing hepatic injury with d-galactosamine (400 mg/kg). The chloroform extract of Polygala arvensis at an oral dose of 200 mg/kg and 400 mg/kg exhibited a significant (P<0.001, P<0.01 and P<0.05) protection effect by normalizing the levels of aspartate amino transferase (ASAT, GOT), alanine amino transferase (ALAT, GPT), alkaline phosphatase (ALP), total bilirubin (TB), lactate dehydrogenase (LDH), total cholesterol (TC), triglycerides (TGL), albumin, total protein (TP) which were significantly (P<0.001) increased in rats by treatment with 400 mg/kg i.p. of d-galactosamine. Silymarin (25 mg/kg), a known hepatoprotective drug used for comparison exhibited significant activity (P<0.001).
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PMID:Hepatoprotective activity of the Indian medicinal plant Polygala arvensis on D-galactosamine-induced hepatic injury in rats. 1682 5

Although dietary restriction (DR) is common in modern society, research about hepatic metabolism and the hepatotoxicity induced by DR has been conducted less intensively than that induced by fasting. In the present study, we fed male Wistar rats at five levels of food intake for one day, including conventional feeding (60 kcal), three of DR (45, 30, and 15 kcal), and fasting (0 kcal), and observed the metabolic changes of hepatic cytochrome P450 2E1(CYP2E1) and the hepatotoxicity of chloroform (CHCl(3)) and carbon tetrachloride (CCl(4)). The CYP2E1 content was significantly increased in 15 kcal-food and fasting groups. The hepatic glutathione (GSH) content, which protects the liver from hepatotoxic agents, was depleted in 15 kcal-food and fasting groups. After the challenge by CHCl(3) and CCl(4), the activities of aspartate aminotransferase and alanine aminotransferase, marker enzymes for liver damage, were elevated remarkably at all food groups. Moreover, their activities increased significantly in DR groups, in comparison to the corresponding 60 kcal-food group. After the challenge, the hepatic GSH content was also depleted significantly in 15 kcal-food and fasting groups. CHCl(3) was cleared by hepatic metabolism about 8-10 times faster than that of CCl(4). Similarly, the areas under the blood concentration-time curve of CCl(4) was as much as twice that of the corresponding CHCl(3). In conclusion, when food was restricted to less than half of conventional amount, hepatic metabolism was affected and the hepatotoxicity induced by CCl(4) or CHCl(3) was augmented by, at least in part, CYP2E1 induction and GSH depletion.
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PMID:One-day dietary restriction changes hepatic metabolism and potentiates the hepatotoxicity of carbon tetrachloride and chloroform in rats. 1766 Jul 3

The role of mitochondrial permeability transition (MPT) and oxidative stress in chloroform toxicity was determined in freshly isolated female B6C3F1 mouse hepatocytes. Incubation of chloroform (12 mM) with hepatocytes resulted in cell death (alanine aminotransferase release and propidium iodide fluorescence). Chloroform had volatilized from the incubation and glutathione was depleted by 1 h; however, toxicity was not significantly different between control and chloroform-incubated cells. Hepatocytes were washed and reincubated in fresh media at 1 h. Subsequent reincubation of chloroform-treated hepatocytes resulted in significant toxicity at 3-5 h. Inclusion of the MPT inhibitor cyclosporine A or the antioxidant N-acetylcysteine (NAC) in the reincubation media at 1 h prevented toxicity. Confocal microscopy studies with the dye calcein AM indicated MPT that was blocked by cyclosporine A or NAC. Fluorescence microscopy studies utilizing JC-1 indicated loss of mitochondrial membrane potential, which was also blocked by cyclosporine A or NAC. Dichlorofluorescein fluorescence increased during the reincubation phase, indicating increased oxidative stress, and the increase was blocked by cyclosporine A. Since oxidative stress may occur by peroxynitrite, its role in toxicity was examined. Either of the nitric oxide synthase inhibitors N(G)-methyl-L-arginine (L-NMMA) and 7-nitroindazole (7-NI) at 1 h blocked toxicity. Western blot analysis of hepatocytes for 3-nitrotyrosine in proteins, a biomarker of peroxynitrite, indicated one major nitrated protein at 81 kD. Nitration of this protein was inhibited by cyclosporine A, L-NMMA, 7-NI, or NAC. The data indicate that chloroform-induced cell death occurs in two phases: a metabolic phase characterized by glutathione depletion, and an oxidative phase characterized by MPT and protein nitration.
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PMID:Mechanisms of chloroform-induced hepatotoxicity: oxidative stress and mitochondrial permeability transition in freshly isolated mouse hepatocytes. 1796 65

To identify the hepatoprotective component from the leaves of Cirsium setidens (Compositae), the methanolic extract was divided into two fractions, chloroform and butanol fractions, and their hepatoprotective efficacy was evaluated in a rat model of hepatic injury caused by D-galactosamine (GalN). Hepatoprotective activity was measured by the activity of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Glutathione metabolism was measured via biochemical parameters such as glutathione (GSH), glutathione reductase (GR), gamma-glutamylcysteine synthetase (GCS), glutathione S-transferase (GST), and superoxide dismutase (SOD) levels. We subjected the butanol fraction, which had higher activity, to column chromatography to yield pectolinarin, which was further hydrolyzed to yield pectolinarigenin. Administration (10, 20 mg/kg, p.o.) of the main flavonoid glycoside component, pectolinarin, and its aglycone, pectolinarigenin, for 2 weeks significantly decreased the activity levels of AST, ALT, ALP and LDH, indicating that the two compounds have hepatoprotective activity. Pectolinarin and pectolinarigenin also increased activity levels of GSH, GR, GCS, and GST, as well as SOD. The significant effect was only seen in SOD activity. This suggests that the two components exhibit hepatoprotective activity mainly via SOD antioxidant mechanism.
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PMID:Pectolinarin and Pectolinarigenin of Cirsium setidens Prevent the Hepatic Injury in Rats Caused by D-Galactosamine via an Antioxidant Mechanism. 1837 79

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

Cancers and hepatoprotective prevention using traditional medicines have attracted increasing interest. The aim of our study was to characterize the putative protective effects of ethanol and chloroform extracts of Peganum harmala on thiourea-induced diseases in adult male rat. We seek to determine the effects of these plant extracts on body weight, thyroid and endocrine cancer parameters. In addition the putative hepatoprotective effect was checked by the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the bilirubin level in the blood. Our data show that ethanol and chloroform extracts of Peganum harmala protected the animal against the carcinogenic effects induced by thiourea since neuron-specific enolase (NSE) and thyroglobulin (TG) levels were back to the normal range. In addition, the observed-hepatocytotoxicity after thiourea treatment was greatly reduced (AST and ALT activities were respectively 270 IU/l and 60 IU/l and in the same order of magnitude as in the untreated rats) as well as the bilirubin levels (6 micromol/l) especially for animals receiving the choroform preparation. Therefore we may suggest that extracts of Peganum harmala are efficient to reduce the toxicity induced by thiourea in male rat as far as the above parameters are concerned.
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PMID:Protective effects of Peganum harmala extracts on thiourea-induced diseases in adult male rat. 1883 35

This study was to explore the relationships between personal exposure to 10 volatile organic compounds (VOCs) and biochemical liver tests with the application of canonical correlation analysis. Data from a subsample of the 1999-2000 National Health and Nutrition Examination Survey were used. Serum albumin, total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) served as the outcome variables. Personal exposures to benzene, chloroform, ethylbenzene, tetrachloroethene, toluene, trichloroethene, o-xylene, m-,p-xylene, 1,4-dichlorobenzene, and methyl tert-butyl ether (MTBE) were assessed through the use of passive exposure monitors worn by study participants. The first two canonical correlations were 0.3218 and 0.2575, suggesting a positive correlation mainly between the six VOCs (benzene, ethylbenzene, toluene, o-xylene, m-,p-xylene, and MTBE) and the three biochemical liver tests (albumin, ALP, and GGT) and a positive correlation mainly between the two VOCs (1,4-dichlorobenzene and tetrachloroethene) and the two biochemical liver tests (LDH and TB). Subsequent multiple linear regressions show that exposure to benzene, toluene, or MTBE was associated with serum albumin, while exposure to tetrachloroethene was associated with LDH and total bilirubin. In conclusion, exposure to certain VOCs as a group or individually may influence certain biochemical liver test results in the general population.
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PMID:Examination of the relationships between environmental exposures to volatile organic compounds and biochemical liver tests: application of canonical correlation analysis. 1911 55

The study was designed to evaluate the hepatoprotective activity of different extracts (petroleum ether, chloroform, ethyl acetate, methanol and aqueous) of P. guajava in acute experimental liver injury induced by carbon tetrachloride and paracetamol. The effects observed were compared with a known hepatoprotective agent, silymarin (100 mg/kg p.o.). In the acute liver damage induced by different hepatotoxins, P. guajava methanolic leaf extract (200 mg/kg, p.o.) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin in carbon tetrachloride and paracetamol induced hepatotoxicity. P. guajava ethyl acetate leaf extract (200 mg/kg, p.o.) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase and bilirubin in carbon tetrachloride induced hepatotoxicity whereas P. guajava aqueous leaf extract (200 mg/kg, p.o.) significantly reduced the elevated serum levels of alkaline phosphatase, alanine aminotransferase and bilirubin in carbon tetrachloride induced hepatotoxicity. P. guajava ethyl acetate and aqueous leaf extracts (200 mg/kg, p.o.) significantly reduced the elevated serum levels of aspartate aminotransferase in paracetamol induced hepatotoxicity. Histological examination of the liver tissues supported the hepatoprotection. It is concluded that the methanolic extract of leaves of Psidium guajava plant possesses better hepatoprotective activity compared to other extracts.
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PMID:Comparative evaluation of different extracts of leaves of Psidium guajava Linn. for hepatoprotective activity. 2006 61


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