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)

The acute hepatic effects of coumarin (2H-1-benzopyran-2-one) in male Wistar rats and Mongolian gerbils has been compared. A single dose of coumarin (125 mg/kg, intraperitoneally (i.p.)) was hepatotoxic to rats within 24 h as assessed by its effects on a variety of hepatic parameters. Coumarin-induced hepatotoxicity was associated with significant increases in relative liver weight, plasma alanine and aspartate aminotransferase activities and hepatic non-protein sulphydryl groups. Cytochrome P-450 content and 7-ethoxycoumarin O-deethylase and glucose 6-phosphatase activities were significantly lower in coumarin-treated compared with control rats. Centrilobular necrosis was only observed in two out of six rats at this dose, but was present in all four coumarin-treated rats when the dose was increased to 150 mg/kg. In contrast to the effects observed in the rat, no evidence was found for coumarin-induced hepatotoxicity in gerbils following a single i.p. dose of 125 mg/kg. These data indicate that the gerbil is less sensitive to the hepatotoxic effects of coumarin than the rat.
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PMID:Species differences in the hepatotoxicity of coumarin: a comparison of rat and Mongolian gerbil. 172 61

To test further the competence of the cirrhotic liver to metabolize vitamin D3 at C-25, hepatocytes were isolated from controls and from CCl4-induced cirrhotic rat livers, as well as from partially hepatectomized rats. The transformation of D3 into 25-hydroxyvitamin D3 was studied in the presence of 10(7) hepatocytes at D3 concentrations of 20 nmol/L to 15.4 mumol/L. Histologically, micronodular cirrhosis was present in all CCl4-treated rats, whereas controls had normal livers; portal venous pressure (p less than 0.008) and intrahepatic collagen content (p less than 0.0001) were significantly increased in CCl4-treated rats, whereas no difference was found between the two groups in the total and ionized serum calcium, D3 metabolites, ALT, AST and alkaline phosphatase. Cytochrome P-450 was 0.27 +/- 0.02 and 0.25 +/- 0.02 nmol/10(6) hepatocytes in controls and cirrhotic rats (N.S.), and it significantly increased in both groups after phenobarbital or 3-methylcholanthrene administration (p less than 0.0001). 25-Hydroxyvitamin D3 formation was best described by power law equations and varied between 0.02 +/- 0.0004 and 29.57 +/- 2.8 in controls, and 0.024 +/- 0.0004 and 32.0 +/- 7.0 pmol.hr-1.10(6) hepatocytes-1 in cirrhotic rats. No statistically significant difference was found in the slopes of the 25-hydroxyvitamin D3 formation, but the y-axis intercept was found to be lower in cirrhotic rats under basal resting conditions (p less than 0.005). Inducers of the mixed function oxidases significantly increased 25-hydroxyvitamin D3 formation in controls as well as in cirrhotic rats (p less than 0.005). Moreover, both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore A23187 and parathyroid hormone. Partial hepatectomy was also without effect on the activation of D3. Furthermore, the cell sequestration of D3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers. The data indicate that in well-compensated micronodular cirrhosis, the C-25 hydroxylation of D3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity.
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PMID:In micronodular cirrhosis, hepatocytes retain a normal C-25 hydroxylation capacity toward vitamin D3: a study using the rat carbon tetrachloride-induced cirrhotic model. 184 94

The purpose of this investigation was to determine the effects of experimental dicrocoeliosis on the hepatic oxidative drug-metabolizing system in hamsters. Studies were carried out 80 and 120 days after infestation with an oral dose of 40 metacercariae of Dicrocoelium dendriticum. The parasitic pathology was ascertained by detection of the fluke eggs in faeces, increased serum alanine aminotransferase and aspartate aminotransferase activities, and postmortem and histological findings. Cytochrome P-450 concentration, aniline hydroxylase activity and ethoxycoumarin O-deethylase activity were significantly decreased in both groups of infected animals. Aminopyrine N-demethylase activity and erythromycin N-demethylase activity were only reduced 120 days after infection. Effects on drug metabolizing enzymes were unrelated to changes in the physical state of the microsomal membrane, as assessed by measurement of fluorescence polarization. The results of this study indicate that the capacity of the liver for handling drugs and xenobiotics may be impaired as a consequence of dicrocoeliosis.
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PMID:Effects of experimental dicrocoeliosis on oxidative drug metabolism in hamster liver. 898 69

The continuous intragastric enteral feeding protocol in the rat was a major development in alcohol-induced liver injury (ALI) research. Much of what has been learned to date involves inhibitors or nutritional manipulations that may not be specific. Knockout technology avoids these potential problems. Therefore, we used long-term intragastric cannulation in mice to study early ALI. Reactive oxygen species are involved in mechanisms of early ALI; however, their key source remains unclear. Cytochrome P-450 (CYP)2E1 is induced predominantly in hepatocytes by ethanol and could be one source of reactive oxygen species leading to liver injury. We aimed to determine if CYP2E1 was involved in ALI by adapting the enteral alcohol (EA) feeding model to CYP2E1 knockout (-/-) mice. Female CYP2E1 wild-type (+/+) or -/- mice were given a high-fat liquid diet with either ethanol or isocaloric maltose-dextrin as control continuously for 4 wk. All mice gained weight steadily over 4 wk, and there were no significant differences between groups. There were also no differences in ethanol elimination rates between CYP2E1 +/+ and -/- mice after acute ethanol administration to naive mice or mice receiving EA for 4 wk. However, EA stimulated rates 1.4-fold in both groups. EA elevated serum aspartate aminotransferase levels threefold to similar levels over control in both CYP2E1 +/+ and -/- mice. Liver histology was normal in control groups. In contrast, mice given ethanol developed mild steatosis, slight inflammation, and necrosis; however, there were no differences between the CYP2E1 +/+ and -/- groups. Chronic EA induced other CYP families (CYP3A, CYP2A12, CYP1A, and CYP2B) to the same extent in CYP2E1 +/+ and -/- mice. Furthermore, POBN radical adducts were also similar in both groups. Data presented here are consistent with the hypothesis that oxidants from CYP2E1 play only a small role in mechanisms of early ALI in mice. Moreover, this new mouse model illustrates the utility of knockout technology in ALI research.
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PMID:CYP2E1 is not involved in early alcohol-induced liver injury. 1060 Aug 24

The serum and hepatic enzymes of rats were studied after exposed to country made liquor (CML) along with two chelating agents (glutathione and Selenium). There was a significant increase in several serum enzyme levels (viz., aspartate transaminase, alanine transaminase, alkaline phosphatase, sorbitol dehydrogenase, glutamate dehydrogenase, bilirubin) and decrease in various hepatic enzymes (Succinic dehydrogenase, Glucose 6-phosphatase, 5'Nucleotiease, Acid phosphatase, Acid ribonuclease, Cytochrome P-450) due to repeated administration of CML (2ml/100g of body weight). Results of this study revealed that the GSH and Se could give a significant protective action in serum and hepatic enzymes of CML exposed rats.
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PMID:Biochemical activity of selenium and glutathione on country made liquor (CML) induced hepatic damage in rats. 2310 62