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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tolerance to several toxic effects of Cd, including lethality, has been shown following pretreatment with Cd. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity. Rats were challenged with Cd (2.0, 3.0, 4.0, or 5.0 mg/kg, iv) 24 hr after pretreatment with saline (2 ml/kg, sc) or Cd (2.0 mg/kg, sc). Ten hours following challenge, plasma enzyme activities were dramatically elevated in control rats (sorbitol dehydrogenase 30- to 300-fold and aspartate aminotransferase 3- to 40-fold). In addition, histologic examination revealed moderate to severe hepatic injury, evidenced by cell swelling, cytoplasmic eosinophilia, pyknosis, karyorrhexis, and necrosis. In Cd-pretreated rats, plasma enzyme levels were similar to control values and only slight morphologic changes were evident. This tolerance to Cd-induced hepatotoxicity is probably due to the increase in hepatic metallothionein induced by Cd pretreatment, which has been shown to alter the hepatic subcellular distribution of Cd such that less binds to subcellular organelles and more binds to metallothionein located in the cytosol.
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PMID:Tolerance to cadmium-induced hepatotoxicity following cadmium pretreatment. 674 Jun 80

Because the concentration of metallothionein (MT) in perinatal rat liver is 10 to 20 times higher than levels present in liver of untreated adult rats, it was of interest to determine if immature rats are less susceptible to the hepatotoxic effects of cadmium (Cd) seen in adults. Male Sprague-Dawley adult rats received a hepatotoxic dose of 4.0 mg Cd/kg, iv, and 10-day-old rats received 4.0, 5.0, 6.0 mg Cd/kg, iv. Ten hours following Cd injection, plasma enzyme activities in adults were elevated (aspartate aminotransferase, 50-fold; sorbitol dehydrogenase, 87-fold) and histologic examination showed extensive hepatic injury; however, no damage was evident in 10-day-old rats, even at the 6 mg Cd/kg dose. Two hours after injection of 3.5 mg Cd/kg, iv (7 microCi 109Cd/mg Cd), the concentration of Cd was higher in liver, heart, and brain and lower in kidneys of 10-day-old rats compared to adults. An age comparison of the hepatic subcellular distribution of Cd revealed a higher amount of Cd in cytosol and less in the particulate fraction of 10-day-old rats. Furthermore, cytosolic Cd was predominantly bound to MT. These data support the hypothesis that presynthesized levels of MT are important in producing tolerance to acute Cd toxicity and that tolerance results from an altered hepatic subcellular distribution of Cd.
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PMID:Resistance to cadmium-induced hepatotoxicity in immature rats. 674 Jun 82

The purpose of this experiment was to compare the toxic effects of aflatoxin B1 (AFB1) and warfarin in pigs and to determine whether these have an additive effect in these pigs fed dietary Cd. Cadmium was provided daily through the diets of 2 concentrations (0 or control, and 83 micrograms/g of diet) during the 40 days of the experiment. At the start of the 5th week, AFB1 and warfarin were given in 5 daily doses (each dose 0.2 mg/kg of body weight) and the effects were determined for 10 days (starting with the 1st treatment day). Aflatoxin B1 given to the pigs fed the control diet (0 Cd) was toxic, inducing significantly increased alkaline phosphatase, sorbitol dehydrogenase, and aspartate aminotransferase activities and the prothrombin time (PT) and activated partial thromboplastin time (APTT) and significantly decreased values in serum total protein, alpha-globulin, beta-globulin, gamma-globulin, and fibrinogen. There was no effect on blood urea nitrogen. The treatment with warfarin was more effective in producing earlier and significantly longer PT and APTT. In the pigs fed the diet with the added Cd, differences in activity of alkaline phosphatase, sorbitol dehydrogenase, aspartate aminotransferase values, but not blood urea nitrogen, as well as differences in intensity and duration of response in PT and APTT occurred when pigs were dosed daily for 5 days after AFB1 or warfarin. It is concluded that dietary Cd (83 micrograms/g of diet) in young pigs has an inhibitory effect on AFB1 toxicity and an enhancing synergistic effect with warfarin.
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PMID:Toxicology of aflatoxin B1, warfarin, and cadmium in young pigs: clinical chemistry and blood coagulation. 680 74

The activity of serum enzymes, such as, creatine kinase (CK), pyruvate kinase (PK), aldolase (ALD), lactate dehydrogenase (LDH), sorbitol dehydrogenase (SbDH), malate dehydrogenase (MDH), glutamate-aspartate aminotransferase (AST), glutamate-alanine aminotransferase (ALT), myokinase (MK), glucosephosphate isomerase (GPI), alkaline phosphatase (AlkP), pseudocholinesterase (PsCHE) isocitrate dehydrogenase and gamma-glutamyltranspeptidase (gamma-GTP), was determined in 256 patients with progressing myodystrophy (PMD) (Duchenne's form in 125, Becker's form in 14, pelvicohumeral form in 36, humeroscapulofacial form in 19, ocular form in 10, other rare forms in 34, and nonidentified forms in 13 patients). In the control group (64 men, 56 women and 50 children), the activity of the enzymes was found to depend on the patients' sex and age. With regard to both parameters, i. e. the degree of the enzyme activity rise and the frequency of the pathological values the most informative were CK, then PK and ALD, and then all the other enzymes. Of all the PMD forms the enzymatic activity appeared to be the highest in patients with the pseudohypertrophic malignant form. By determining the activity of five enzymes (CK, ALD, LDH, AST and ALT) and taking into consideration the patient's age, the onset and the duration of the disease one can distinguish between sick and healthy subjects, as well as between various forms of PMD.
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PMID:[Serum enzyme dynamics in progressive muscular dystrophies]. 703 17

A high energy maize diet produced a higher incidence of fatty liver-haemorrhagic syndrome than a low energy barley diet when the diets were fed during the summer. The triglyceride content of the liver increased with the liver haemorrhage score and in hens with the highest scores there was evidence of hepatic hyperplasia. They also had high activities of aspartate transaminase and cholinesterase in the plasma and a low activity of sorbitol dehydrogenase. There was no increase in plasma endotoxin levels as the syndrome developed or any significant variation in these levels with the haemorrhage score, the triglyceride content of the liver or plasma enzyme activities. It was concluded that the steatosis does not impair the ability of the liver to inactivate endotoxins of enteric bacteria and that these toxins are not involved in the pathogenesis of the syndrome.
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PMID:Bacterial endotoxins and the pathogenesis of fatty liver--haemorrhagic syndrome in the laying hen. 732 74

Chlordecone (Kepone) amplification of CCl4 toxicity occurs at small, nontoxic levels of chlordecone and CCl4 and results in highly increased irreversible hepatotoxicity culminating in lethality. Although it is generally assumed that CCl4 lethality is due to hepatic failure, no definitive studies are available in the literature bridging massive liver failure and death. The present studies were designed to evaluate whether hepatic failure is the cause of the lethality during chlordecone-amplified CCl4 toxicity. Male Sprague-Dawley rats were maintained on control or a chlordecone (10 ppm) diet for 15 days and injected with CCl4 (100 microliters/kg, ip) on Day 16. Rats were killed at 0, 6, 12, 24, 36, and 48 hr after CCl4 challenge. Hepatic failure was evaluated by measuring plasma glucose, ammonia, bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), sorbitol dehydrogenase (SDH), hepatic ATP, glycogen, and by histological and histomorphometric analyses. Plasma creatinine, urea, and kidney histopathology were also assessed for possible renal injury. As expected CCl4 administration to chlordecone-pretreated rats resulted in 20% lethality by 36 hr, which progressed with time, and all rats died within 72 hr. A significant and progressive hypoglycemia was observed with a 60% reduction in plasma glucose at 48 hr. Hepatic glycogen content dropped precipitously. Similarly, hepatic ATP levels remained suppressed (80% of control) at all the time points studied. Plasma ammonia levels were significantly elevated, and by 48 hr, a threefold increase was observed. Plasma ALT, AST, SDH, and bilirubin increased progressively until the death of rats receiving the chlordecone + CCl4 combination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic failure leads to lethality of chlordecone-amplified hepatotoxicity of carbon tetrachloride. 750 40

Dietary exposure to a nontoxic level of chlordecone (10 ppm for 15 days) followed by a single exposure to a subtoxic dose of CCl4 (100 microliters/kg, ip) is known to result in a 67-fold amplification of CCl4 toxicity. The hypothesis that the underlying mechanism is due to incapacitation of hepatocytes leading to an ablation of the early-phase hormetic response of tissue repair as a consequence of precipitous decline in hepatic glycogen and ATP, received experimental support from Mehendale in 1990. The present study was designed to investigate if direct administration of ATP to rats maintained on the chlordecone diet would result in protection from the hepatotoxic and lethal effects of the chlordecone+CCl4 combination. Male Sprague-Dawley rats (125-150 g) were maintained either on a diet containing no added contaminants (control) or on a diet containing 10 ppm chlordecone for 15 days, and were challenged with CCl4 (100 microliters/kg, ip) on day 16. Without ATP administration all rats died within 72 h, while administration of ATP (100 mg/rat, sc) to chlordecone-pretreated rats at -1, +1, 3, 5, 12, 24 and 36 h of CCl4 injection resulted in 100% survival. Injection of ATP, at -1, +1, 3 and 5 h of CCl4 administration to chlordecone pretreated rats decreased plasma enzyme elevations (alanine and aspartate aminotransferase, sorbitol dehydrogenase) as well as substantially preventing elevation of plasma bilirubin levels at 6, 12 and 24 h. Hepatic ATP levels were also elevated at 6 and 12 h, but not at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine triphosphate protection of chlordecone-amplified CCl4 hepatotoxicity and lethality. 751 59

The effect of oral administration of praziquantel at different dose levels on the activities of metabolizing hepatic enzymes (aminopyrine N-demethylase, aniline 4-hydroxylase and UDP-glucuronyltransferase) was studied in healthy locally bred rabbits. The pathological changes resulting from drug's toxicity were assessed histologically, by measurement of total plasma protein concentration and of the activities of the plasma enzymes sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST). No significant changes were obtained after praziquantel administration at dose levels of 40 and 800 mg/kg body weight, whereas 1600 mg/kg and 2000 mg/kg of praziquantel resulted in a significant decrease in the activities of the three drug-metabolizing hepatic enzymes under investigation in the livers of treated rabbits. All rabbits which received praziquantel at the dose rate of 2000 mg/kg died 10-20 hours following praziquantel treatment.
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PMID:The effect of praziquantel on the activities of some drug-metabolizing hepatic enzymes in rabbits. 760 Sep 44

Male Sprague-Dawley rats maintained on either normal diet (N) or on a diet containing phenobarbital (PB; 225 ppm) or mirex (M; 10 ppm) for 15 days received either corn oil or 1 single administration of a protective dose of CCl4 (0.3 ml/kg, po) on day 16. At 24, 48, 72, 96, or 144 hr after the protective dose, a high dose of CCl4 (5 ml/kg, po) was administered to rats of all the groups, and they were observed for 14-day lethality. In a second experiment, in rats maintained on N, PB, or M diet, liver microsomal cytochromes P-450, aminopyrine demethylase, and aniline hydroxylase were measured at various time points after the administration of the protective dose of CCl4. Serum aspartate transaminase, alanine transaminase, and sorbitol dehydrogenase elevations and histopathological changes observed under a light microscope were used as toxic end points to assess hepatotoxicity. Autoprotection was 100% when the high dose was given at 24 hr after the protective dose in N rats, whereas it was only 55% in PB- or M-pretreated rats. For later time points of 48, 72, and 96 hr, autoprotection was only around 50% in N rats, whereas it was almost 100% in PB- and M-pretreated rats. When the high dose was administered at 144 hr after the protective dose, autoprotection further declined to 25% in N rats and to 75% in M-treated rats, but it remained at 100% in PB-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of phenobarbital and mirex pretreatments on CCl4 autoprotection. 781 19

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that causes massive centrilobular hepatic necrosis at high doses, leading to death. The objectives of this study were to test our working hypothesis that preplaced cell division and hepatic tissue repair by prior thioacetamide (TA) administration provides protection against APAP-induced lethality and to investigate the underlying mechanism. Male Sprague-Dawley rats were treated with a low dose of TA (50 mg/kg, intraperitoneally [i.p.]) before challenge with a 90% lethal dose (1,800 mg/kg, i.p.) of APAP. This protocol resulted in a 100% protection against the lethal effect of APAP. Because TA caused a 23% decrease of hepatic microsomal cytochromes P-450, the possibility that TA protection may be caused by decreased bioactivation of APAP was examined. A 30% decrease in cytochromes P-450 induced by cobalt chloride failed to provide protection against APAP lethality. Time course of serum enzyme elevations (alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase) indicated that actual infliction of liver injury by APAP peaked between 12 to 24 hours after the administration of APAP, whereas the ultimate outcome of that injury depended on the biological events thereafter. Although liver injury progressed in rats receiving only APAP, it regressed in rats pretreated with TA. Acetaminophen t1/2 was not altered in TA-treated rats, indicating that significant changes in APAP disposition and bioactivation are unlikely. Moreover, hepatic glutathione was decreased to a similar extent regardless of TA pretreatment, suggesting that decreased bioactivation of APAP is unlikely to be the mechanism underlying TA protection. [3H]Thymidine incorporation studies confirmed the expected stimulation of S-phase synthesis, and proliferating cell nuclear antigen studies showed a corresponding stimulation of cell division through accelerated cell cycle progression. Intervention with TA-induced cell division by colchicine antimitosis ended the TA protection in the absence of significant changes in the time course of serum enzyme elevations during the inflictive phase of APAP hepatotoxicity. These studies suggest that hepatocyte division and tissue repair induced by TA facilitate sustained hepatic tissue repair after subsequent APAP-induced liver injury, producing recovery from liver injury and protection against APAP lethality.
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PMID:Stimulated hepatic tissue repair underlies heteroprotection by thioacetamide against acetaminophen-induced lethality. 784 22


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