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)

Hepatic stimulator substance was extracted from the liver of weanling Sprague-Dawley rats according to the method of LaBrecque. Quang-Ming mice were injected with carbon tetrachloride to induce acute liver failure. Hepatic stimulator substance suppressed the elevation of ALT and AST induced by carbon tetrachloride in a dose-dependent manner. Hepatic histological changes indicated that hepatic stimulator substance reduced the severity of hepatic lesion induced by carbon tetrachloride and reversed carbon tetrachloride-induced reduction of hepatic mitochondrial succinic dehydrogenase activity. In attempting to elucidate the mechanism or mechanisms of this protective effect, we found that hepatic stimulator substance significantly restored the carbon tetrachloride-induced decrease of hepatocyte plasmalemma and mitochondrial and microsomal membrane fluidity. Hepatic stimulator substance also decreased the malondialdehyde content of carbon tetrachloride-intoxicated mice; restored the liver-reduced glutathione content, which was lowered by carbon tetrachloride intoxication; stimulated liver regeneration, as shown by enhanced DNA synthesis; and increased the 3H-thymidine incorporation into DNA of hepatocytes. We propose that hepatic stimulator substance protects the liver against acute liver failure induced by carbon tetrachloride poisoning, probably by an antioxidative effect on hepatocyte membrane lipid peroxidation, which was increased by free radicals produced from carbon tetrachloride. In addition, hepatic stimulator substance stimulates hepatocyte proliferation. These protective mechanisms may act in concert to protect against carbon tetrachloride injury.
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PMID:Hepatic stimulator substance protects against acute liver failure induced by carbon tetrachloride poisoning in mice. 847 68

Rifampicin conferred significant protection against carbon tetrachloride (CCl4)-induced liver injury. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were not markedly altered and only hepatocellular fatty degeneration was found in mice pretreated with rifampicin (200 mg/kg), whereas severe centrilobular necrosis was observed and serum ALT and AST activities were as high as 281 and 271 I.U./l, respectively, in the control group following administration of CCl4 (400 microliters/kg). The contents and activities of microsomal drug-metabolizing enzymes in rifampicin-pretreated animals were also much higher than those of the controls. CCl4-mediated malondialdehyde (MDA) formation was increased in rifampicin-treated liver microsomes, demonstrating that rifampicin was capable of increasing the NADPH-dependent metabolism of CCl4 catalyzed by P-450 2E1 to produce free radicals. However, MDA formation was obviously depressed by rifampicin at varying concentrations from 2 to 32 x 10(-6) M in an in vitro cytochrome P-450 (P-450) enzyme system. On the other hand, NADPH oxidation in the metabolism of CCl4 and aniline hydroxylation were not suppressed in the presence of rifampicin in this systems, suggesting that rifampicin did not influence the biotransformation of CCl4 by P-450 2E1 in vitro. Therefore, the protective effect of rifampicin against CCl4 hepatotoxicity appeared to result from the direct inhibition of lipid peroxidation generated by CCl4-derived free radicals.
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PMID:Protective effect of rifampicin against acute liver injury induced by carbon tetrachloride in mice. 878 35

Planar PCB congeners are embryotoxic and teratogenic to birds including American kestrels. The developmental toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) was studied in the posthatching kestrel as a model for the eagle. Nestlings were dosed orally for 10 days with 5 microl/g body weight of corn oil (controls) or the planar PCB 126 at concentrations of 50, 250, or 1000 ng/g body weight. Dosing with 50 ng/g of PCB 126 resulted in a hepatic concentration of 156 ng/g wet weight, liver enlargement and mild coagulative necrosis, over 10-fold increases in hepatic microsomal ethoxyresorufin-O-dealkylase and benzyloxyresorufin-O-dealkylase, and approximately a 5-fold increase in methoxyresorufin-O-dealkylase. At this dose, mild to moderate lymphoid depletion of the spleen was apparent, as were decreased follicle size and content of the thyroid. At 250 ng/g, concentration of PCB 126 in the liver was 380 ng/g with increasing multifocal coagulative necrosis, decreased bone growth, decreased spleen weight with lymphocyte depletion of the spleen and bursa, and degenerative lesions of the thyroid. At 1000 ng/g, the liver concentration was 1098 ng/g, accompanied by decreased bursa weight, decreased hepatic thiol concentration, and increased plasma enzyme activities (ALT, AST, and LDH-L) in addition to the previous effects. Highly significant positive correlations were noted between liver concentrations of PCB 126 and the ratio of oxidized to reduced glutathone. These findings indicate that nestling kestrels are more susceptible to PCB 126 toxicity than adults, but less sensitive than embryos, and that planar PCBs are of potential hazard to nestling birds.
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PMID:Developmental toxicity of PCB 126 (3,3',4,4',5-pentachlorobiphenyl) in nestling American kestrels (Falco sparverius). 895 49

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

To determine the clinical, biochemical, and histological features, and outcome of childhood autoimmune hepatitis (AIH), we reviewed the medical records of 52 children with AIH, 32 (median age: 10 [2-15] years) anti-nuclear and/or smooth muscle antibody (ANA/SMA) positive, 20 (7 [0.8-14] years) liver/kidney microsomal antibody (LKM-1) positive, with median follow-up of 5 years (range 0.3-19). At presentation: 56% had symptoms of prolonged acute hepatitis; LKM-1 positive were younger (P = .011), with higher bilirubin (P = .007), and AST (P = .047); ANA/SMA positive had lower albumin (P = .023); 69% ANA/SMA positive, and 38% LKM-1 positive were cirrhotic (P = .080). ANA/SMA positive had increased frequency of HLA haplotype A1/B8/DR3/DR52a compared with controls (53% vs. 14%, P < .001). Of six (5 LKM-1 positive) with fulminant hepatitis, four were transplanted, one died, and one ANA/SMA positive improved with immunosuppression. Of 47 treated with immunosuppression, 2 (1 LKM-1 positive) died with no remission and 4 (2 LKM-1 positive) were transplanted 8 to 14 years after diagnosis. Immunosuppression was stopped successfully in 19% of ANA/SMA positive after a median of 3 years of treatment, but in none of LKM-1 positive. Baseline bilirubin and international normalized prothrombin ratio (INR) were independent variables predictive of outcome. In conclusion, ANA/SMA positive and LKM-1 positive AIH in childhood have clinical, biochemical, and histological differences, but similar severity and long-term outcome.
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PMID:Autoimmune hepatitis in childhood: a 20-year experience. 904 95

The association between an in vivo oxidative stress condition of the liver and hepatic porphyria during HCB intoxication is postulated. After 30 days of treatment, HCB (25 mg/kg b.w.) promotes an induction of microsomal cytochrome P450 system, increase in microsomal superoxide anion generation accompanied by increased levels of liver lipid peroxidation, as measured by the production of thiobarbituric acid reactants and by spontaneous visible chemiluminescence. Concomitantly, liver antioxidant defenses are slightly modified, with decreased activity of glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase contributing to an oxidative stress condition of the liver. These liver biochemical alterations are closely related to increased levels of urinary coproporphyrin, plasma AST and ALT activities and to the onset of liver morphological lesions.
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PMID:Pro- and anti-oxidant parameters in rat liver after short-term exposure to hexachlorobenzene. 919 4

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.
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PMID:Time courses of hepatic injuries induced by chloroform and by carbon tetrachloride: comparison of biochemical and histopathological changes. 933 1

Administration of Aflatoxin B1 (AFB1) with safflower seed oil to hubbard chickens caused a significant increase in liver microsomal protein, electron transport components, and drug metabolizing enzymes. No alteration was observed in the activity of alanine and aspartate aminotransferases. AFB1 treatment with dimethylsulfoxide (DMSO) as a vehicle caused a significant decrease in electron transport components, drug metabolizing enzymes, and a significant increase in the activity of aspartate aminotransferase. Higher inhibition was observed at 1.5 mg/kg dose level of AFB1. Inhibition by AFB1 was maximal after 24 hr of treatment and decreased thereafter. AFB1 treatment with DMSO caused no significant change in electron transport components and drug metabolizing enzymes in Rhode Red Island (RRI) strain. Vancob male chickens showed significant decrease in electron transport components and drug metabolizing enzymes, while a significant increase was observed in vancob females. Results suggest that the effects of AFB1 depend on treatment vehicle, strain and sex of chickens.
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PMID:Effects of aflatoxin B1 on liver microsomal enzymes in different strains of chickens. 944 Feb 43

Preliminary short-term toxicity studies of sucrose acetate isobutyrate (SAIB) in the dog demonstrated that addition of this additive to the diet was associated with an increase in liver size and elevated serum alkaline phosphatase activity with no evidence of pathological change by light microscopy. To determine the basis for these changes, a 12-week oral toxicity study of SAIB was conducted in the dog and a similar study was performed in the rat. SAIB was fed in the diet to groups of six beagle dogs of each sex at 0, 0.5, 1.0, 2.0 and 4.0%. SAIB was also fed to groups of 40 Sprague-Dawley rats of each sex at levels of 0, 2.5, 5.0 and 10.0%. In the rat study, in addition to routine toxicology parameters, hepatic microsomal enzyme induction was determined using a zoxazolamine hypnotic test, urinary ascorbic acid excretion and determination of hepatic carboxylesterase activity. Sodium phenobarbital was fed to groups of 20 rats of each sex at a dose of 100 mg/kg body weight/day by gavage as a positive control for hepatic microsomal enzyme induction. In the dog study, routine toxicological tests were supplemented by tests for bromsulfophthalein (BSP) retention, histochemical staining of liver sections for glycogen, phosphorylase, succinate dehydrogenase, and acid and alkaline phosphatases. Levels of liver lipid, protein, glycogen and carboxylesterase activity were also determined. Electron microscopic examinations were made on liver sections from the dog study at the end of the 12-week SAIB feeding period and after a 2-week withdrawal period. Administration of SAIB to rats did not reveal evidence of any effect on hepatobiliary function, and there was no indication of microsomal enzyme induction. Body weight gain of male rats fed SAIB was decreased, probably as the result of decreased palatability of the diet; SAIB did not affect body weight gain in females. The changes observed in the dogs fed SAIB included increased serum alkaline phosphatase activity with no change in serum alanine aminotransferase, aspartate aminotransferase or lactic dehydrogenase activity and no change in serum electrolyte, serum protein, glucose or bilirubin levels. No haematological changes were observed. BSP retention was observed at all SAIB dose levels. There were no SAIB-related pathological changes in any organ when examined by light microscopy. Examination by electron microscope revealed dilatation of bile canaliculi and an increase in smooth endoplasmic reticulum compared with controls. Histochemical studies also indicated increased enzyme activity of the bile canaliculi. The electron-microscope-revealed changes were completely reversed during a 2-week treatment withdrawal period. The dog study did not establish a no-effect level for changes in hepatobiliary function induced by feeding SAIB.
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PMID:Subchronic toxicity studies of sucrose acetate isobutyrate (SAIB) in the rat and dog. 951 48

The hepatocellular necrogenic and regenerative responses of newly weaned rats (21 days old) to a sublethal dose of thioacetamide (6.6 mmol kg-1) were studied in comparison to adult (6-month old rats), in terms of liver injury, antioxidant defense systems and cell proliferation. Hepatocellular necrosis, detected by serum aspartate aminotransferase, was less severe in newly weaned rats than in adult animals and was parallel to previous changes in the activity of microsomal FAD monooxygenase system responsible for thioacetamide biotransformation. Liver damage in hepatocytes from newly weaned rats was also detected by the decreased levels of glutathione and protein thiol groups (47%, p < 0.001 and 52%, p < 0.001 vs. untreated, respectively) and by the enhanced malondialdehyde production (334%, p < 0.001) and glutathione S-transferase activity (384%, p < 0.001). No significant differences were detected in these values when compared to adults. Changes in cytosolic and mitochondrial superoxide dismutase and catalase activities in hepatocytes from newly weaned rats at 24 h, following thioacetamide (49%, p < 0.001; 50% and 53%, p < 0.001 vs. untreated, respectively), were less severe against those in adult hepatocytes at 48 h of intoxication, and the increases in glutathione peroxidase and glutathione reductase activities were significantly lowered: 25% (p < 0.001) and 41% (p < 0.001), respectively. Post-necrotic DNA synthesis in hepatocytes from newly weaned rats peaked at 48 h of intoxication, while in adults a more intense peak appeared at 72 h preceded by a sharp decrease in tetraploid population. These differences indicate that the lower necrogenic response against the same dose of thioacetamide in newly weaned rats may be due to the lower rate of thioacetamide biotransformation and to the earlier onset of cell division. Accordingly, the growing liver from newly weaned rats presents advantages against the necrogenic aggression of thioacetamide, first, because the diminished activity of its specific microsomal detoxification system, and second because the earlier increase in the proliferative response prevents the progression of injury permitting an earlier restoration of liver function.
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PMID:Necrogenic and regenerative responses of liver of newly weaned rats against a sublethal dose of thioacetamide. 960 62


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