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)

To examine the combined hepatotoxic and nephrotoxic effects of cadmium and ethanol, rats maintained on an ethanol containing liquid diet (5% w/w) were given cadmium either acutely (3 x 1 mg/kg IP) or subacutely (about 14 mg/kg/day PO for 6 weeks). Parameters tested were cadmium, zinc and copper contents of blood and various organs, metallothionein (MT) contents, polysome profile of liver and kidneys, serum SDH and GPT levels and creatinine clearance. Ethanol reduced the hepatic MT contents without altering the polysome profile and the zinc and copper contents. Cadmium on the other hand raised the MT contents in liver and kidneys. This effect of cadmium predominated in the combined treatment. Morphological examination and functional tests (SDH, GPT, creatinine clearance) indicate that cadmium does not enhance the toxic effects of ethanol, and vice versa.
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PMID:Investigation into the combined effects of ethanol and cadmium on rat liver and kidneys. 227 4

The present experiments were designed to study the effect of chronic ethanol consumption on endotoxin toxicity. The intravenous injection of endotoxin produced a more pronounced increase of serum AST and ALT activities in chronic ethanol-fed rats, when compared to controls. The activities of hepatic mitochondrial enzymes, succinate dehydrogenase and cytochrome oxidase, were also distinctly decreased by endotoxin treatment in chronic ethanol-fed rats. Consistent with these biochemical alterations, light and electron microscopic examinations revealed severe liver injury after endotoxin injection in chronic ethanol-fed rats. Furthermore, the increase of blood BUN and creatinine levels accompanied by the degeneration of the renal tubulus and slight infiltration of neutrophils into the glomerule were produced by endotoxin treatment and were more conspicuous in chronic ethanol-fed rats than controls. Therefore, the biochemical and histological evidence indicates that endotoxin markedly potentiates organ injury after chronic ethanol consumption. In addition, a more pronounced decrease in blood antithrombin III activity accompanied by an increase in fibrin degradation product level in blood was recognized in chronic ethanol-fed rats receiving endotoxin, when compared to controls receiving endotoxin. This increase of blood fibrin degradation product level correlated well with the decrease of antithrombin III activity (r = -0.6116; p less than 0.005). These findings of blood antithrombin III activity and fibrin degradation product level indicate that the coagulation-fibrinolysis system is more activated by endotoxin treatment after chronic ethanol consumption. Furthermore, the activation of the coagulation-fibrinolysis system was well correlated with biochemical and histological alterations representing hepatorenal involvement.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endotoxin-induced hypercoagulability: a possible aggravating factor of alcoholic liver disease. 254 Oct 59

The increase in serum gamma-glutamyl transpeptidase (GGT) is a well known marker of chronic alcoholism in man. We have previously shown that ethanol (180 mM) induces GGT activity 2-3-fold in the C2 rat hepatoma cell line. In this study, we have analyzed the interaction of ethanol with steroid hormones and drugs in this well defined cell culture system. Dexamethasone (100 nM), a synthetic glucocorticoid agonist, completely prevented the induction of GGT by ethanol, but had no effect when added alone. This inhibitory effect was also observed with other corticosteroids, but not with sex steroids; it was prevented by RU 486, a glucocorticoid antagonist. These observations suggest that dexamethasone acts through a high affinity glucocorticoid receptor. Conversely, ethanol did not interfere with the glucocorticoid induction of alanine aminotransferase in the same cell. We have analyzed the metabolism of ethanol in the C2 cells. These cells lack significant alcohol dehydrogenase activity as well as any cytochrome P-450 Alc immunoreactivity. Dexamethasone did not modify the disappearance of ethanol in the culture medium of those cells. We conclude that glucocorticoid hormones interact with ethanol at the cellular level, and that this interaction does not involve a modification of alcohol metabolism.
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PMID:Glucocorticoid hormones prevent the induction of gamma-glutamyl transpeptidase by ethanol in a rat hepatoma cell line. 256 56

To determine if impaired intestinal absorption contributes to the folate deficiency observed in chronic alcoholics, we assessed in vivo folate absorption in Hanford mini-pigs fed ethanol with an adequate diet. Sixteen minipigs were pair-fed diets supplemented with ethanol or sucrose to 60% of total calories for 11 mo. In the ethanol-fed pigs peak blood alcohol concentrations averaged 28 mmol/L, serum alanine transaminase and aspartate transaminase activities were elevated, and liver histology showed a centrilobular distribution of succinate dehydrogenase. Tissue folate concentrations were comparable in both groups. The jejunal uptake of folic acid, measured by intestinal perfusion, was similar in both groups of animals and was not affected by acute exposure to 445 mmol/L ethanol. The in vivo hydrolysis of polyglutamyl folate was reduced by 35% in one ethanol-fed minipig. Decreased hydrolysis of polyglutamyl folate may represent an early step in the development of folate deficiency in chronic alcoholics.
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PMID:Folate absorption in alcoholic pigs: in vivo intestinal perfusion studies. 259 32

As part of a multicenter V.A. Cooperative Study, 437 male veterans with varying stages of alcoholic liver injury were followed over a 4.5 year period. Their ethnic distribution consisted of 256 Caucasians, 109 black Afro-Americans, 63 Puerto Rican Hispanics, and 9 Native American Indians. Survival analyses revealed significant differences between groups (P = 0.0002): 66% of Afro-Americans were still living at 42 months; Caucasians were intermediate with 40% survival; and only 28% of Hispanics were alive. The number of Native American Indians enrolled was too small to draw conclusions but none of those enrolled survived beyond 24 months. Survival regression analysis of 30 clinical, laboratory, histologic and nutritional parameters, revealed the following significant risk factors: clinical severity (P less than 0.0001), histologic severity (P less than 0.0001), race (P = 0.001), age (P = 0.002), BUN (P = 0.01) and ALT (P = 0.02). These analyses indicated that ethnicity, independent of other variables, is significantly associated with outcome from the disease.
Alcohol Alcohol 1989
PMID:Longevity among ethnic groups in alcoholic liver disease. 264 88

Endotoxemia frequently appears in severe type of alcoholic liver disease. However, we have little knowledge how endotoxin influences the progression of alcoholic liver injury. Thus, to study the causal mechanism for the progression to the severe type of alcoholic liver diseases, endotoxin (0.2 mg/100 g BW, E. Coli O26:B6) was intravenously injected in chronic ethanol-fed rats and controls, and then, rats were sacrificed after 16 hours of endotoxin treatment. The elevation of serum GOT and GPT activities induced by endotoxin was significantly higher in chronic ethanol-fed rats than controls, and these biochemical changes were well correlated with the grade of necrosis of liver histology. Furthermore, in chronic ethanol-fed rats, endotoxin treatment tremendously increased blood BUN and creatinine levels and produced the degeneration of renal tubuli with neutrophil infiltration into glomerulus. These experimental findings are very similar to the severe type of alcoholic liver disease. On the other hand, endotoxin significantly decreased serum values of CH50 in chronic ethanol-fed rats, but not in controls. Such alterations of CH50 induced by endotoxin were well correlated with the several parameters indicating the injury of liver and kidney. Therefore, the present study may indicate that chronic ethanol ingestion aggravates endotoxin-induced organ injury, and that the activation of complement system may associate with such progression of organ injury.
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PMID:[An experimental study on the severe type of alcoholic liver disease--a pathogenetic role of potentiated activation of complement system by endotoxin after chronic ethanol consumption]. 267 43

We studied the relationship between the ratio of serum aspartate aminotransferase (ASAT) to alanine aminotransferase (ALAT) and histologic changes in human and experimental alcoholic liver disease. The patient population included 52 hospitalized patients enrolled in a Veterans Administration Cooperative study. The experimental animal group consisted of male Wistar rats fed an ethanol-liquid diet. Of the 52 patients with alcoholic hepatitis, 33 had evidence of cirrhosis. The mean +/- SD for the ASAT/ALAT ratio in the group with alcoholic hepatitis and no cirrhosis was 1.47 +/- 0.84, the mean +/- SD in the group with hepatitis and cirrhosis was significantly higher (2.68 +/- 1.32, p less than 0.01). There was no difference in the ratio between the rats with and without liver fibrosis. The cause for the increased ASAT/ALAT ratio in serum in the presence of cirrhosis is unknown and may reflect more severe liver damage.
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PMID:Serum aspartate aminotransferase to alanine aminotransferase ratio in human and experimental alcoholic liver disease: relationship to histologic changes. 270 13

Two groups of experimental animals with pair-fed controls were studied to evaluate the effect of chronic carbon monoxide (CO) exposure on progression of experimental alcoholic liver injury. Eight pairs of male Wistar rats were continuously infused liquid diet and ethanol or isocaloric dextrose for four months. Four pairs were also exposed to CO. Liver damage was followed monthly by serum ALT and morphologic assessment of liver biopsy. Serum levels of ALT were significantly higher in the CO-ethanol group compared to other groups. Electron microscopy revealed a greater degree of cell necrosis in the CO exposed group which explained the significantly higher ALT activity in these animals. Both experimental groups (CO-ethanol and air-ethanol) had significantly greater liver damage than controls. Carboxyhemoglobin levels were not different in the ethanol-fed and control group. Our results show that chronic CO exposure enhances liver cell necrosis in ethanol-fed rats thereby lending support to the hypothesis that ethanol and hypoxia enhance cellular disruption in the liver which could be important in the pathogenesis of alcoholic liver disease in rats.
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PMID:Effect of chronic carbon monoxide exposure on experimental alcoholic liver injury in rats. 279 87

To better define the significance and mechanism of acetaldehyde-mediated transaminase inhibition, acetaldehyde metabolism was studied in rat liver homogenates and cytosols. When either preparation was incubated at 37 degrees with 1.5 mM acetaldehyde for 4 hr, acetaldehyde levels fell rapidly in the first 30 min and little inhibition of aspartate aminotransferase (GOT) or alanine aminotransferase (GPT) resulted. In contrast, incubation with 50 mM ethanol also resulted in a peak acetaldehyde level of 1.0 to 1.5 mM by 2 hr, but this level was then maintained for the next 2 hr and transaminases were inhibited by 20-35%. Sequential addition of low dose (125-250 microM) pulses of acetaldehyde to rat liver preparations resulted in a progressive decrease in the rate of acetaldehyde disappearance. When the pulsing schedule was adjusted accordingly to maintain acetaldehyde levels between 50 and 250 microM for 8 hr, transaminases were again inhibited by 20-40%. Finally, addition of 1-5 mM pyridoxal and pyridoxal 5'-phosphate, aldehydic B6 vitamers, to cytosols 2-4 hr after pulsing with acetaldehyde was begun, almost completely prevented further transaminase inhibition. In contrast, the non-aldehydic B6 vitamers, pyridoxine, pyridoxamine and pyridoxamine 5'-phosphate, did not affect acetaldehyde-mediated transaminase inhibition. These findings suggest that (1) prolonged exposure to low levels of acetaldehyde impairs acetaldehyde metabolism in rat liver homogenates and cytosols; (2) acetaldehyde toxicity may be more dependent on sustained exposure to acetaldehyde than on the peak level of acetaldehyde attained; and (3) aldehydic B6 vitamers can modify on-going acetaldehyde-mediated transaminase inhibition.
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PMID:Inhibition of rat liver transaminases by low levels of acetaldehyde and the pharmacologic effects of B6 vitamers. 281 34

Plasma-HDL-cholesterol levels were determined in 104 patients (92 males and 12 females) with a mean age of 43 years (range 20-70 years). All were admitted to a clinic for alcoholics and had a mean drinking history of 13 years with a mean consumption of 48.2 l of pure ethanol per year. There was no correlation between HDL-cholesterol level and the total ethanol consumption in the year before admission or in the month before admission. However, weak negative correlations between HDL-cholesterol and smoking habits (r= -0.26, P less than 0.001) and body weight (r= -0.34, P less than 0.001) were found. In 40 patients the mean HDL-cholesterol level decreased from 1.94 +/- 0.75 mmol/l (SD) at admission to 1.29 +/- 0.36 mmol/l after 16 days of abstinence. Altogether, 33 (31.6%) of 104 patients had a HDL-cholesterol level above our reference value of 2 mmol/l while alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and gamma-glutamyltranspeptidase (GGT) were increased in 49, 52.9 and 70.3%, of the cases respectively. Although screening programmes have shown an association between plasma-HDL-cholesterol and the number of drinks consumed per day, no such association could be found in a sample of alcoholics. Decrease of HDL-cholesterol during abstinence, however, seems to be a marker in alcoholics.
Alcohol Alcohol 1985
PMID:Plasma-HDL-cholesterol and estimated ethanol consumption in 104 patients with alcohol dependence syndrome. 286 25


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