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)

Subchronic treatment of male rats with carbon tetrachloride (CCl4, twice weekly 0.2 ml/kg p.o.) and feeding a 5% alcohol solution instead of drinking water led to a nearly complete liver cirrhosis in all animals within 4 weeks. This was also documented by a three fold increase in hepatic total hydroxyproline content. Steatosis was quantified by enhanced liver triglyceride concentrations and acute necroses by increments of serum enzyme activities (GPT, SDH). Daily oral treatment with malotilate (100 mg/kg) totally prevented the development of liver cirrhosis, hepatic hydroxyproline accumulation and increases in serum enzyme activities induced by CCl4-alcohol. In cianidanol-treated rats (100 mg/kg p.o.) only portoseptal fibrosis was seen, however hydroxyproline and triglyceride accumulation as well as enhanced serum enzyme activities were not suppressed. D-penicillamine (300 mg/kg p.o.) and colchicine (50 micrograms/kg i.p.) failed to protect rats against CCl4-alcohol induced fibrosis, necrosis and steatosis in this model.
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PMID:Hepatoprotection by malotilate against carbon tetrachloride-alcohol-induced liver fibrosis. 376 14

An experimental model for monitoring rat liver function during protracted exposure to hepatotoxic agents is proposed. Owing to their invasiveness, the models usually employed are appropriate for studying the mechanism of action of toxic substances, but do not allow the liver situation to be followed over the course of time. The need to sacrifice animals to determine liver triglycerides-one of the key parameters in the progress of toxic damage- reduces the possibility of following such progress in the same animals. This study describes the testing of a model for monitoring three basic parameters of liver injury: cytolysis, steatosis and metabolic deficiency of the liver. CCl4 has been chosen as model-hepatotoxin. Steatosis is determined by evaluating the triglyceride content of small specimens of liver, obtained through open-field biopsies, which appear to be representative of the whole liver. Fatty liver is paralleled by the block in Triton-induced hypertriglyceridaemia. Determination of serum triglycerides derives from a very poorly invasive technique which can be repeated several times. The combination of these tests with the assessment of both the cytolysis (ALT and SDH release into the circulation) and the impairment of the efficiency of liver microsomal enzymes (TMO clearance), seems to offer a reliable experimental procedure in predicting the hepatotoxic effect of xenobiotics.
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PMID:A model for monitoring changes in liver function. 379 13

Toxicity of the antioxidant dodecyl gallate was studied in 150-day experiments on male white rats. The antioxidant was administered intragastrically in doses of 250, 50 and 10 mg/kg bw. The general status and behavior of the animals, the survival rate, weight gain, peripheral blood, the amount of urea, total serum protein, soluble proteins of the liver and kidneys, and activity of enzymes (AST, ALT, LDH, SDH, glucose-6-phosphate dehydrogenase, alkaline and acid phosphatase of the serum, liver and kidneys, the weight of the internal organs) were studied over time, followed by morbid anatomy studies. Quantitative determination of serum lipids (total fats, total cholesterol, esterified cholesterol, free cholesterol, triglycerides, free fatty acids, triglycerides plus free fatty acids, and phospholipids) was made on the 150th day after the onset of experiments. When administered in a dose of 250 mg/kg, dodecyl gallate produced death of the animals and an increase in the content of triglycerides plus free fatty acids, a decrease in the weight of the spleen and morphological alterations in the liver, kidneys and spleen. The dose 50 mg/kg was also toxic. It brought about changes in the activity of serum and liver AST, an increase in the content of TF, TG, FFA, TG plus FFA and phospholipids, a reduction in the weight of the spleen and pathological changes in the liver, kidneys and spleen. The dose 10 mg/kg is regarded as liminal.
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PMID:[Toxicological study of the long-term effects of the antioxidant dodecyl gallate on albino rats]. 400 81

In this study, we tested a new artificial liver device using liver pieces in 8-h hemoperfusion of comatous porcine blood and compared two alternative tissue preparations. Acute hepatic coma in the pigs was induced by complete devascularization of the liver. The animals were killed in stage IV coma (15-25 h after the operation), and 1 l blood was perfused over 200 g fresh or DMSO-preserved liver cubes. After the devascularization GOT, GPT, GLDH, AP, LDH, SDH, bilirubin, free fatty acid, and bile acid levels in serum increased progressively. Ammonia concentrations underwent a rapid increase in the first 9 h of coma development from 126.0 +/- 9.9 to 321.9 +/- 62.2 mumol/l. Most of the amino acids in serum were elevated and molar ratio of BCAA/AAA declined from 3.87 +/- 0.79 to 0.92 +/- 0.24. In the course of hemoperfusion ammonia was removed from the perfusate to 71% of the initial values using fresh and to 39% using preserved tissue. Correspondingly, there was an increase in urea concentrations. Amino acid metabolism was ameliorated during the perfusion; Fischer's quotient increased from 0.91 +/- 0.15 to 1.38 +/- 0.14 (fresh liver) and from 0.89 +/- 0.14 to 2.11 +/- 0.44 (preserved liver); neuroexcitatory amino acids Asp and Glu were markedly elevated. Energy charge of the liver cells increased and reached levels exceeding 0.5 in both experimental groups, a balanced energy metabolism was maintained and suggests active metabolization by the liver pieces. In comparison with fresh tissue, preserved liver cubes proved effective. We consider our artificial liver device capable of temporary hepatic support in acute necrosis of the liver and suppose that its efficiency can be potentiated by combining this system with other procedures.
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PMID:Successful treatment of hepatic coma by a new artificial liver device in the pig. 408 14

Treatment of male rats with carbon tetrachloride (CCl4, 2 x weekly 0.2 ml/kg p.o.) and a 5% alcohol solution, instead of drinking water, for 4 weeks led to marked increases in serum enzyme activities (GOT, GPT, SDH), hepatic triglyceride and hydroxyproline content. Diethyl dithiocarbamate (dithiocarb, 200 mg/kg p.o.) simultaneously applied with CCl4 totally suppressed the elevation in serum enzyme activities and hepatic hydroxyproline concentration, and partially suppressed that of the triglyceride content. (+)-Catechin (50-300 mg/kg p.o.) simultaneously applied with CCl4 had no influence on the enhanced serum enzymes, but depressed the augmented content of both hepatic triglyceride and hydroxyproline in a dose-dependent way. The most effective dose with respect to the reduction of the hydroxyproline concentration was 100 mg/kg (+)-catechin; the highest dose (300 mg/kg), however, enhanced the CCl4-alcohol-induced hydroxyproline augmentation.
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PMID:Effects of dithiocarb and (+)-catechin against carbon tetrachloride-alcohol-induced liver fibrosis. 629 80

To study the relationship between lipid peroxidation and cellular damage we studied three compounds known to evoke lipid peroxidation (cumene hydroperoxide, CHP), hepatocellular injury (thioacetamide, TAA) or both (carbon tetrachloride, CCl4). Phenobarbital-induced male rats were treated with one of the three agents and lipid peroxidation was monitored via the measurement of exhaled ethane. Treatment with both, CCl4 and CHP resulted in an increased ethane expiration, whereas TAA did not. When liver-specific serum enzyme activities (GPT, SDH) were investigated 24 h later, however, hepatotoxicity was evident only in rats treated with either CCl4 or TAA. The ATP-dependent Ca2+-sequestration activity of microsomal membranes, suggested to be a final common pathway leading to cellular death, was studied in microsomes isolated from rats treated with either agent. 2 h after treatment with CCl4 or TAA a clear inhibition was seen which persisted after 24 h in the case of CCl4 only. CHP did not affect the Ca2- -pump activity. Thus, a clear correlation between cellular damage and lipid peroxidation cannot be expected in every case. An impairment of the microsomal calcium-pump, however, seems to be a crucial event which leads to hepatocellular injury.
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PMID:Interrelationship between in vivo lipid peroxidation, microsomal Ca2+-sequestration activity and hepatotoxicity in rats treated with carbon tetrachloride, cumene hydroperoxide or thioacetamide. 662 17

The effect of rolitetracycline (50 micrograms/g i.v.) alone or in combination with ethinylestradiol (0.1 and 1.0 micrograms/g s.c. once daily for 4 days) on liver function (BSP retention, serum GPT and SDH) and histomorphology was investigated in mice. Rolitetracycline alone increased liver weight, BSP-retention and serum GPT levels. Ethinylestradiol at the lower dose tended to enhance the BSP retention and the morphological changes of the liver produced by rolitetracycline but had no additional effect on the serum GPT and on liver weight. In contrast, hepatotoxic effects of the higher dose of ethinylestradiol were not further enhanced by rolitetracycline.
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PMID:Investigation into the combined hepatotoxicity of rolitetracycline and ethinyloestradiol. 662 65

Liver damage was investigated in rat using serum enzyme activities measurements. Responses were recorded 24 h after whole body inhalation exposure to vapors of bromobenzene, carbon tetrachloride, chloroform, o-dichlorobenzene, 1,2-dichloroethane and dimethylformamide as model toxicants. First, rats were exposed during a single 4 h period to different concentrations of each solvent and the minimally active concentration was determined. Second, repeated exposures to chemicals at this concentration level (6 h daily, 2 or 4 days) were used in order to examine whether hepatotoxicity was enhanced. GLDH and SDH are more sensitive and more constant indices than GOT and GPT. It appears that a single exposure period induced more marked serum activities enhancement than repeated exposures.
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PMID:Short-term inhalation test for evaluating industrial hepatotoxicants in rats. 665 18

Twelve different enzyme activities, which are listed and explained in greater detail in Table 2, were determined statistically secured, and discussed, following a three-year study into arterial plasma of 118 female and 124 male minks, aged between six and seven months and kept under anaesthesia. Simply normally distributed or logarithmically distributed plasma enzyme activities were found to differ primarily by sex, with other experimental conditions being identical and regular. The enzyme activities of ICDH, active CPK, and total LDH (the latter only with females) were normally distributed, whereas all the other enzymes activities tested, except for gamma-GT and SDH, were of Gaussian distribution only after logarithmic transformation of the individual values. The plasma enzyme activities of GPT, LAP, ChE, LDH1, MDH, and AP differed from those of GOT, gamma-GT, SDH, total LDH and active CPK, in that they usually exhibited highly significant sex-related differences. All minks were tranquilised and kept under general anaesthesia, using neuroleptanalgesia, but all their enzyme activities were found to vary just as widely as those reported elsewhere in literature, in the context of minks without anaesthesia. The latter result was experimentally confirmed by means of a model experiment in which enzyme activities were recorded from nine male ferrets, prior to, during, and after neuroleptanalgesia.
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PMID:[Morphology and biochemistry of blood of various mustelids. 3. Enzymographic studies of arterial plasma of mink (Mustela vison Schreber, 1777)]. 701 Dec 44

The normal level of human serum alcohol dehydrogenase (EC 1.1.1.1) (ADH) activity which is not measurable by conventional methods was found to be within the range 0.07-0.56 U/1 when measured by a sensitive method based on a coenzyme recycling reaction. In different liver diseases the normal upper limit of serum ADH activity was found to be exceeded up to 70 times. Although ADH activity under pathological conditions usually parallels that of other enzymes, e.g., sorbitol dehydrogenase (EC 1.1.1.14) (SDH) and alanine transaminase (EC 2.6.1.2) (ALT), its relative elevation above the upper normal limit is generally greater, particularly in the early stages of viral hepatitis. Observations on some patients also suggested that very early stages of liver damage, caused by drugs or secondary malignancy, could be detected by increases of serum ADH activity when the activities of some other liver specific enzymes were still within their normal values. A pilot experiment on rats, intoxicated with carbon tetrachloride, showed that serum ADH activity could reflect acute liver parenchymal damage more sensitively than SDH and ALT activity.
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PMID:Serum alcohol dehydrogenase activity in liver diseases. 703 78


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