Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbon tetrachloride (CCl4) added to isolated rat hepatocytes produces toxic effects which were assessed by monitoring the release of aspartate aminotransferase (ASAT). CBrCl3 was equitoxic with CCl4, while CHCl3 was inactive, suggesting solvent properties not to be involved. The CCl4-mediated toxicity was markedly decreased by carbon monoxide, indicating possible activation by cytochrome P 450. 55 flavonoid compounds were tested for their ability to interfere with CCl4-induced release of ASAT. The compounds are cianidanol, 3-ethers and 3-esters thereof, flavanones, flavanolols, flavones and flavanols. The more hydrophilic compounds inhibit the CCl4-induced toxicity, while the lipophilic derivatives are potentiators. No other structure-activity relationships are apparent. The results are discussed in terms of the mechanisms of action of the compounds and of the validity of the technique as a screening test for hepatotropic agents.
 ...
PMID:Inhibiting or potentiating effects of flavonoids on carbon tetrachloride-induced toxicity in isolated rat hepatocytes. 377 62

There is increasing evidence to show that drug metabolism and effects are modulated by biological rhythms; therefore the possibility that chloroform (CHCl3) induced acute hepatotoxicity may also vary as function of time of administration was investigated in male Sprague--Dawley rats. The animals were given a single intraperitoneal dose of CHCl3 or saline, 0.5 ml/kg, at 09:00 h, 13:00 h, 17:00 h, 21:00 h or 03:00 h and killed 4 h after treatment. The hepatotoxicity induced by CHCl3 was determined by the serum glutamic-pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT) and lactic dehydrogenase (LDH) activities and by the glucose-6-phosphatase (G6Pase) activity of the liver. The increases in SGPT, SGOT and LDH were minimal and maximal when the organic solvent was injected at 09:00 h and 21:00 h, respectively, whilst the activity of G6Pase was depressed significantly at 03:00 h and 13:00 h under similar conditions. Starving the rats for 16 h prior to the injection of CHCl3 at 09:00 h increased substantially the hepatotoxicity as measured by the above enzyme activities. These findings may be relevant in the toxicity of CHCl3 in industrial workers exposed to this solvent at various times of the day.
 ...
PMID:Temporal variations in chloroform-induced hepatotoxicity in rats. 685 99

Twenty-three chemicals, differing widely in cytotoxic (hepatotoxic) potency in vivo, were examined to determine their ability to release glutamic-oxaloacetic transaminase (GOT) from hepatocytes isolated by a nonperfusion method from rat liver. The test chemicals were carbon tetrachloride, chloroform, 1,1,2- and 1,1,1-trichloroethane, six bromobenzene analogs, tri-n-butyl tin, chlorpromazine, tetracycline, halothane, phenobarbital, L-ethionine, acetaminophen, thioacetamide, allyl alcohol, ethanol, ascorbic acid, dimethyl sulfoxide, and acetone. In all but two cases--thioacetamide and allyl alcohol--there was a good correspondence between chemicals active in the assay as now performed and those that elevate serum transaminase and cause liver injury on short-term exposure in vivo. These results indicate that with further effort it may be possible to develop an effective, inexpensive, and rapid prescreen to identify drugs and environmental chemicals that are potentially cytotoxic to animals and humans.
 ...
PMID:Evaluation of hepatocytes isolated by a nonperfusion technique in a prescreen for cytotoxicity. 699 12

The formation of free radicals after orthotopic liver transplantation in the rat correlates with graft failure. Fatty livers from alcoholics transplant poorly, so these studies were designed to examine the effect of alcohol on free radical formation in a rearterialized rat liver transplantation model. Treatment of rats for 3-5 weeks with either a high-fat or an ethanol-containing liquid diet caused characteristic pericentral lipid accumulation. After storage in University of Wisconsin cold storage solution (UW) and transplantation, a reperfusion injury characterized by increased postoperative AST levels (greater than 1500 U/l in about 3 hours) was observed in rats fed high-fat or alcohol-containing diets, whereas parenchymal cell injury was seen much less in low-fat controls. Survival was around 63% in the low-fat group but decreased to 12 and 18% in the high-fat and alcohol groups, respectively. Furthermore, intracellular lipid content correlated inversely with survival. In untransplanted livers, the spin trap alpha-phenyl N-tert-butylnitrone (PBN) was infused, and blood samples were collected and extracted with chloroform:methanol. Signals indicative of carbon-centered PBN radical adducts were barely detectable in all untransplanted groups studied by electron paramagnetic resonance. In contrast, a robust 6-line complex spectrum was obtained from all groups studied immediately after 48 hours of cold storage in UW solution and transplantation. A mixture of 3 radical species was identified. Two had coupling constants similar to lipid-derived free radicals, whereas the third is a new species with unique coupling constants and is most likely oxygen derived. In low-fat controls, the signal was reduced significantly by superoxide dismutase (SOD)/catalase; however, SOD/catalase had no effect on free radicals in lipid-loaded livers. Thus, both dietary high fat and alcohol exposure produce a unique SOD/catalase-insensitive free radical species that may be involved in the mechanism of failure of fatty livers after orthotopic liver transplantation.
 ...
PMID:Primary nonfunction of fatty livers produced by alcohol is associated with a new, antioxidant-insensitive free radical species. 788 90

A pilot study addressed potential effects of long-term exposure to chlorination products in swimming pools. The indicator compound chloroform was detectable in blood from competitive swimmers in an indoor pool (mean = 0.89 +/- 0.34 microgram/l; n = 10), but not in outdoor pool swimmers. No hepatotoxic effect was indicated by serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) or gamma-glutamyl transpeptidase (gamma-GT) enzyme levels. beta-2-microglobulin, an indicator of renal damage, was significantly elevated in urine samples of the slightly, but significantly, younger indoor swimmers. The precise ratio between these 2 possible causes, age and chloroform exposure, as well as the mechanism of the former, remain to be elucidated.
 ...
PMID:Swimming pool chlorination: a health hazard? 791 Dec 64

Chloroform (CHCl3) is widely used in the manufacture of drugs, cosmetics, plastics and cleaning agents. It is also found in chlorinated drinking water. This study was designed to investigate the toxic effect of CHCl3 on isolated male rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and the cell viability was determined by Trypan blue exclusion. The leakage of cytosolic enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) after treatment with CHCl3 was measured. Reduced glutathione content (GSH) and its related enzymes, glutathione reductase (GSH-Rx) and glutathione peroxidase (GSH-Px), were also evaluated to study the effect of CHCl3 on hepatocytes. Exposure to 100 and 1000 ppm CHCl3 results in a significant decrease in cell after 30 min incubation. However, the effect of 1 and 10 ppm concentrations was observed at 60 min incubation. AST leakage was significantly increased in all treatment groups, while ALT was significantly increased at 100 and 1000 ppm CHCl3 after 60 and 30 min, respectively. As early as 15 min, GSH was decreased significantly at 1000 ppm, but at 100 and 10 ppm CHCl3 the decrease in GSH began after 30 and 120 min, respectively. GSH-Px activity did not changed. However, the activity of GSH-Rx was significantly decreased at 1000 ppm CHCl3 and at the same time GSH content was decreased. The data indicate that the toxic effect of CHCl3 was dose- and time-dependent. The degree of GSH depletion correlated with increased cytotoxicity and decreased GSH-Rx activity due to CHCl3.
 ...
PMID:The mechanism of chloroform toxicity in isolated rat hepatocytes. 835 69

The hepatoprotective effect of various fractions (n-hexane, CHCl3, EtOAc, n-BuOH, and H2O) of Ban-zhi-lian derived from Scutellaria rivularis Benth was studied against carbon tetrachloride (CCl4), D-galactosamine (D-GalN) and acetaminophen (APAP)-induced acute hepatotoxicity in rats. Liver damage was assessed by quantifying serum activities of glutamate oxaloacetate transaminase (sGOT) and glutamate pyruvate transaminase (sGPT), as well as by histopathological examination. The results indicated that the CHCl3 fraction and EtOAc fractions exhibited the greatest hepatoprotective effects on CCl4-induced liver injuries, the CHCl3 fraction and n-hexane fraction are most potent against D-GalN-induced intoxication, and the CHCl3 fraction represented the most liver-protective effect on APAP-induced hepatotoxicity. The pathological changes of hepatic lesions caused by these three hepatotoxicants were improved by treatment with the fractions mentioned above, which were compared to Glycyrrhizin (GLZ) and Silymarin as standard reference medicines.
 ...
PMID:Hepatoprotective effect of the fractions of Ban-zhi-lian on experimental liver injuries in rats. 920 8

The relationship was investigated between biochemical and morphological changes in chloroform (CHCl3)- and carbon tetrachloride (CCl4)-induced liver damage. The time courses of hepatic microsomal cytochrome P450 (CYP) content, hepatic microsomal CYP2E1 activity, hepatic reduced glutathione (GSH) content, plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were examined in relation to the liver morphology in rats orally treated with CHCl3 or CCl4 (3.35 mmol/kg). The CYP content and the activity of CYP2E1 markedly decreased in the CCl4-treated rats 3 h after treatment compared to much lower decreases in the CHCl3-treated rats. The hepatic GSH content was decreased to a similar extent in both groups of rats at 3 h after treatment; in the CCl4-treated rats, the GSH content continued to decrease, reaching a minimum at 24 h and without attaining the normal level at 72 h after treatment. By contrast, hepatic GSH content in the CHCl3-treated rats began to increase from 6 h, attaining complete recovery 48 h after treatment. Plasma ALT and AST activities were significantly elevated by CCl4 as early as 3 h after treatment, while the activities in the CHCl3-treated rats did not increase until 6 h after treatment. In both groups of rats, ALT and AST activities reached a maximum at 24 h, and gradually decreased, remaining at abnormal levels at 72 h. Hepatic cells in the CCl4-treated rats were found to be necrotic as early as 3 h post-treatment, whereas few or no morphological changes appeared in the liver of CHCl3-treated rats. The extent of necrosis was at a maximum 24 h after treatment in both CHCl3- and CCl4-treated rats. In addition, some necrotic cells remained in the liver of CCl4-treated rats 72 h after treatment, while the necrosis in the CHCl3-treated rats was almost negligible. The present results indicate that almost the same time-courses of biochemical and morphological changes were followed in rats of both the CHCl3- and CCl4-treated groups.
 ...
PMID:Time courses of hepatic injuries induced by chloroform and by carbon tetrachloride: comparison of biochemical and histopathological changes. 933 1

Effects of a single dose of betaine on the chloroform-induced hepatotoxicity were examined in adult male ICR mice. Administration of betaine (1000 mg/kg, ip) 1 to 7 hr prior to a chloroform challenge (0.25 ml/kg, ip) resulted in remarkable enhancement of hepatotoxicity as indicated by increases in serum sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. The potentiation of hepatotoxicity was most significant when mice were treated with betaine 4 hr earlier than chloroform. However, a 24 hr prior administration of betaine protected the animals from induction of the chloroform hepatotoxicity. Thus, its effect appeared to be highly dependent on the time lapse from the betaine pretreatment to the challenge of mice with chloroform. Betaine treated either 4 or 24 hr prior to sacrifice did not alter the hepatic contents of cytochrome P-450, cytochrome b5, or NADPH cytochrome P-450 reductase activity. Accordingly the hepatic microsomal p-nitroanisole O-demethylase, aminopyrine N-demethylase, or p-nitrophenol hydroxylase activities were not influenced by the betaine pretreatment. Betaine was shown not to affect any of the enzyme activities associated with glutathione (GSH) conjugation reaction, such as glutathione S-transferases (GSTs), glutathione disulfide (GSSG) reductase and GSH peroxidase irrespective of the time of its administration. When betaine was administered to mice 2-6 hr prior to sacrifice, hepatic GSH level, but not plasma GSH, was decreased significantly. Enhancement of the chloroform hepatotoxicity by betaine correlated well with the reduction in hepatic GSH levels. Both hepatic and plasma GSH levels were elevated in mice 24 hr following the betaine treatment. The results suggest that betaine affects induction of the chloroform hepatotoxicity by modulating the availability of hepatic GSH, which appears to be associated with its role in the transsulfuration pathway in the liver.
 ...
PMID:Effects of singly administered betaine on hepatotoxicity of chloroform in mice. 973 16

Chloroform (CHCl3) and bromodichloromethane (BDCM) are generally the two most prevalent disinfection by-products formed during chlorination of drinking water, and both have been shown to be hepatotoxic, nephrotoxic, and carcinogenic in rodents. As the toxicity of these trihalomethanes (THMs) has most often been studied with corn oil as the vehicle of administration, the objectives of this study were to assess hepatotoxicity after exposure to single, low dosages of CHCl3 and BDCM given orally in an aqueous vehicle to estimate a lowest-observed-adverse-effect level (LOAEL) and a no-observed-adverse-effect level (NOAEL) and to compare toxic potency. Ninety-day-old male Fischer 344 rats were gavaged with either 0.125, 0.1875, 0.25, 0.5, 0.75, 1.0, or 1.5 mmol CHCl3 or BDCM/kg body weight in 10% Alkamuls EL-620 (5 ml/kg body weight). At 24 h postgavage, serum was collected for analysis of clinical chemistry indicators of liver damage. Both CHCl3 and BDCM induced dose-dependent hepatotoxicity; serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase were elevated significantly over control at 1.5, 1.0, and 0.5 mmol/kg. At these dose levels after 24 h, the two THMs appeared to be equipotent hepatotoxicants. Additional assessments at later time points demonstrated that BDCM causes more persistent liver damage than CHCl3 (Lilly et al., 1997). At 0.25, 0. 1875, and 0. 125 mmol of either THM/kg, significant increases over control were not detected for any measured endpoint. Therefore, these data indicate that the acute, oral NOAELs and LOAELs for liver toxicity are 0.25 and 0.5 mmol/kg, respectively, for both CHCl3 and BDCM. These determinations should provide a basis to establish new exposure limits for One-Day Health Advisories for these prevalent THMs.
 ...
PMID:NOAEL and LOAEL determinations of acute hepatotoxicity for chloroform and bromodichloromethane delivered in an aqueous vehicle to F344 rats. 974 4


<< Previous 1 2 3 4 5 6 Next >>