Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Solanum alatum Moench. has been shown to have a protective effect against carbon tetrachloride (CCl4)-induced liver injury. Solanum alatum treatment (100 mg/kg, p.o.) decreased the elevation of serum alanine aminotransferase (ALT; GPT) and aspartate aminotransferase (AST; GOT) induced by acetaminophen (paracetamol) (600 mg/kg, i.p.) administration. It also decreased the extent of visible necrosis in liver tissue. In addition, Solanum alatum treatment restored hepatic glutathione (GSH) depletion induced by acetaminophen (600 mg/kg, i.p.) administration. Microsomal enzyme levels such as P-450, reductase, and aniline hydroxylation enzyme were also restored to normal levels after Solanum alatum administration. The hepatoprotective mechanism may function through direct binding with acetaminophen toxic metabolites, decreasing the attraction of acetaminophen metabolites for other cellular GSH or thiol protein. Additionally, Solanum alatum treatment increased the concentration of hepatic GSH and maintained a high level activity of GSTase, which led to acceleration of the excretion of toxic acetaminophen metabolites.
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PMID:The hepatoprotective effects of Solanum alatum Moench. on acetaminophen-induced hepatotoxicity in mice. 1079 22

The effects of thymoquinone (TQ) and desferrioxamine (DFO) against carbon tetrachloride (CCl4)-induced hepatotoxicity were investigated. A single dose of CCl4 (20 microl/kg, i.p.) induced hepatotoxicity, manifested biochemically by significant elevation of activities of serum enzymes, such as alanine transaminase (ALT, EC: 2.6.1.2) , aspartate transaminase (AST, EC: 2.6.1.1) and lactate dehydrogenase (LDH, EC: 1.1.1.27). Hepatotoxicity was further evidenced by significant decrease of total sulfhydryl (-SH) content, and catalase (EC: 1.11.1.6) activity in hepatic tissues and significant increase in hepatic lipid peroxidation measured as malondialdhyde (MDA). Pretreatment of mice with DFO (200 mg/kg i.p.) 1 h before CCl4 injection or administration of TQ (16 mg/kg/day, p.o.) in drinking water, starting 5 days before CCl4 injection and continuing during the experimental period, ameliorated the hepatotoxicity induced by CCl4, as evidenced by a significant reduction in the elevated levels of serum enzymes as well as a significant decrease in the hepatic MDA content and a significant increase in the total sulfhydryl content 24 h after CCl4 administration. In a separate in vitro assay, TQ and DFO inhibited the non-enzymatic lipid peroxidation of normal mice liver homogenate induced by Fe3+/ascorbate in a dose-dependent manner. These results indicate that TQ and DFO are efficient cytoprotective agents against CCl4-induced hepotoxicity, possibly through inhibition of the production of oxygen free radicals that cause lipid peroxidation.
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PMID:Protective effects of thymoquinone and desferrioxamine against hepatotoxicity of carbon tetrachloride in mice. 1088 36

This study examined the effects of black tea (Camellia sinensis L.) on lipid peroxidation and glutathione levels in carbon tetrachloride (CCl4)-treated male Wistar rats. Three groups of rats formed two control groups and one treatment group. The control groups were fed with a standard diet, while the black tea group were fed the standard diet plus 6% by weight dried black tea leaves. After two months, the rats in the black tea group and in one control group were administered a single dose of CCl4 (1 ml/kg, i.p.) and sacrificed two hours later. Rats in the other control group were administered olive oil in a similar fashion. Lipid peroxide levels in liver and plasma, glutathione (GSH) levels in liver and alanine transaminase (ALT) and aspartate transaminase (AST) activities in plasma were measured. Rats in the black tea group were found to have significantly decreased liver lipid peroxide levels, and ALT and AST activities compared with the rats in the CCl4-treated control group. In addition, liver glutathione levels were decreased in the black tea group. These data suggest that black tea attenuates CCl4-induced hepatic injury.
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PMID:Effect of black tea on lipid peroxidation in carbon tetrachloride treated male rats. 1096 44

The pharmacokinetics and hepatoprotective effects of 2-methylaminoethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybip henyl-2-carboxylic acid-2'-carboxylate monohydrochloride (DDB-S) have been investigated in rats with CCl4-induced acute hepatic failure. To study the pharmacokinetics of DDB-S, rats were divided into a control group and a CCl4-intoxicated group. DDB-S 50 mg kg(-1) was administered by intravenous bolus injection to both groups of rats. In the CCl4-intoxicated rats the plasma concentrations of DDB-S were significantly higher, the area under the plasma concentration-time curve from time zero to time infinity was significantly greater (6-46 vs 3.34 mg min mL(-1)), and the total body (7.74 vs 15.0 mL min(-1) kg(-1)), renal (2.55 vs 5.10 mL min(-1) kg(-1)), nonrenal (5.07 vs 9.65 mL min(-1) kg(-1)), and biliary (1.48 vs 2.69 mL min(-1) kg(-1)) clearances were significantly slower compared with the control rats. This could be due to decreased hepatic cytochrome P450 activity and impaired kidney function induced by CCl4. To study the hepatoprotective effects of DDB-S, rats were divided into three groups, control rats and CCl4-intoxicated rats with or without DDB-S pretreatment (50 mg kg(-1) i.p.). The effects of DDB-S pretreatment on CCl4-induced liver injury were considerable; the serum levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase were significantly lower by 54.3, 44.6 and 67.2%, respectively, compared with the CCl4-intoxicated-only group. In an in-vitro study, rat hepatocytes were exposed to fresh medium containing 10 mM CCl4 and various concentrations of DDB-S (10 or 100 microg mL(-1)). The levels of alanine transaminase and aspartate transaminase in the medium were measured as an indicator of hepatocyte injury. DDB-S dose-dependently decreased the levels of alanine transaminase and aspartate transaminase compared with CCl4-intoxication only. These results indicate that DDB-S has hepatoprotective activity.
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PMID:Pharmacokinetics and hepatoprotective effects of 2-methylaminoethyl-4,4'-dimethoxy-5 ,6,5',6'dimethylenedioxybiphenyl-2-carboxylic acid-2'-carboxylate monohydrochloride in rats with CCl4-induced acute hepatic failure. 1104 90

1. The aim of the present study was to develop an experimental model of liver cirrhosis in rabbits using CCl4 and phenobarbital. 2. Liver cirrhosis was induced in male New Zealand white rabbits (n = 10) by intragastric administration of CCl4 once weekly starting 14 days after the addition of phenobarbital to the drinking water (50 mg/day). Controls received phenobarbital only (n = 7). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), albumin and bilirubin levels were determined throughout CCl4 treatment. The initial dose of CCl4 was 20 microg and subsequent doses were calculated to maintain AST and ALT levels between 400 and 800 IU/L for the duration of treatment (16 weeks). Indocyanine green (ICG) clearance was performed before and at the end of CCl4 treatment. Animals were killed at 16 weeks and three fragments of each liver lobe were processed for histological examination. A semiquantitative score was used to evaluate the development of fibrosis. 3. Cirrhosis developed in 80% of rabbits treated with CCl4. These animals did not gain weight compared with controls (P < 0.05). A significant reduction of ICG clearance was observed in CCl4-treated rabbits compared with controls (P < 0.05). The AST, ALT, bilirubin and gamma-GGT levels were elevated in CCl4-treated rabbits. 4. In conclusion, this model is successful in producing liver cirrhosis and may be useful in studies investigating metabolic, immunological or biochemical changes during the evolution of chronic liver disease.
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PMID:Development of an experimental model of liver cirrhosis in rabbits. 1111 35

The effects of black tea (Camellia sinensis L.) on lipid peroxidation and glutathione (GSH) levels in carbon tetrachloride (CCl4)-treated female Wistar rats were examined. Two control groups and one treatment group were tested. The control groups were fed with a standard diet, while the black tea group was fed the standard diet plus 6% by weight dried black tea leaves. At the end of 2 months, a single dose of CCl4 (1 ml/kg, i.p.) in olive oil was administered to rats in one of the control groups and the black tea group. They were sacrificed after 2 hours. Rats in the other control group were administered olive oil in a similar fashion. Measurements were made of lipid peroxide levels in liver and plasma, glutathione levels in liver, and alanine transaminase (ALT) and aspartate transaminase (AST) activities in plasma. Liver lipid peroxide levels, plasma ALT and AST activities were significantly decreased in the black tea group compared with the CCl4-treated control group, while plasma lipid peroxide levels were not. These results are parallel to those previously found with Wistar male rats. Glutathione levels, however, were not significantly affected, in contrast to the data relating to male rats, either after CCl4 or black tea treatments. The results of our study add to the findings that black tea attenuates CCl4-induced hepatic injury but also indicates the susceptibility of glutathione levels to endocrinological effects.
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PMID:Effect of black tea on lipid peroxide and glutathione levels in female rats. 1120 8

The aim of the study was to evaluate the effect of cirrhosis on the disposition of the haemoglobin-based oxygen carrier, diaspirin cross-linked haemoglobin (DCLHb). Cirrhosis was induced in male Sprague-Dawley rats (200-250 g) by inhalational exposure to carbon tetrachloride (CCl4), over a period of 6 weeks. Pharmacokinetic evaluation was performed after a single intravenous bolus administration of DCLHb (400 mg kg(-1)). Serum biochemistry, including aspartate transaminase, alkaline phosphatase, bile acids, serum albumin, and serum creatinine, were measured in CCl4-treated (n = 6) and age-matched control (n = 6) rats. After 6 weeks, the jugular vein and carotid artery were cannulated for bolus DCLHb administration (400 mg kg(-1)) and blood sampling, respectively, in both groups of rats. Cirrhosis produced significant (P < 0.05) elevations in alkaline phosphatase (497.4 +/- 84.8 U L(-1) vs 241.2 +/- 5.1 U L(-1)), aspartate transaminase (920.5 +/- 190.9 U L(-1) vs 238.2 +/- 118.1 U L(-1)) and bile acids (333.8 +/- 77.3 mg dL(-1) vs 43.8 +/- 4.2 mg dL(-1)) compared with the control group. No significant renal dysfunction was observed as a result of CCl4 exposure. Plasma DCLHb concentrations declined approximately log-linearly. Systemic clearance of DCLHb was estimated to be 2.2 +/- 0.7 mL h(-1) in the treatment group and was slightly, but not significantly, less in the control group (3.6 +/- 1.7 mL h(-1)). There was also a trend toward a longer elimination half-life in the treatment group (4.7 +/- 2.2 h) compared with the control group (3.8 +/- 0.8 h), although this difference was not statistically significant. Cirrhosis does not significantly alter the disposition of DCLHb perhaps due to increased extra-hepatic metabolism by the reticulo-endothelial system.
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PMID:Pharmacokinetics of diaspirin cross-linked haemoglobin in a rat model of hepatic cirrhosis. 1127 13

The present study was undertaken to investigate whether or not the hepatoprotective activity of acetylbergenin was superior to bergenin in carbon tetrachloride (CCl4)-intoxicated rat. Acetylbergenin was synthesized by acetylating bergenin, which was isolated from Mallotus japonicus. The hepatoprotective effects of acetylbergenin were examined against CCl4-induced liver damage in rats by means of serum and liver biochemical indices. Acetylbergenin was administered orally once daily for 7 successive days, then a 0.5 ml/kg mixture of CCl4 in olive oil (1:1) was intraperitoneally injected at 12 h and 36 h after the final administration of acetylbergenin. Pretreatment with acetylbergenin reduced the elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma-glutamyltransferase in a dose dependent fashion. Acetylbergenin also prevented the elevation of hepatic malondialdehyde formation and depletion of glutathione content dose dependently in CCl4-intoxicated rats. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored to almost normal levels. The results of this study strongly suggest that acetylbergenin has potent hepatoprotective activity against CCl4-induced hepatic damage in rats by glutathione-mediated detoxification as well as having free radical scavenging activity. In addition, acetylbergenin doses of 50 mg/kg showed almost the same levels of hepatoprotective activity as 100 mg/kg of bergenin, indicating that lipophilic acetylbergenin is more active against the antihepatotoxic effects of CCl4 than those of the much less lipophilic bergenin.
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PMID:Protective effects of acetylbergenin against carbon tetrachloride-induced hepatotoxicity in rats. 1133 30

Acute hepatic failure was induced experimentally in rats by intraperitoneal injection of 2.5 mL kg(-1) carbon tetrachloride (CCl4), and the effects on the expression and function of P-glycoprotein in the liver, kidney and brain were evaluated. The CCl4 injection significantly increased the indicators of hepatic function (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase), but not of renal function (blood urea nitrogen, glomerular filtration rate). In rats with acute hepatic failure, the hepatic P-glycoprotein concentration increased 1.5-fold and the ATP concentration decreased to approximately 40% that in control rats. In contrast, P-glycoprotein concentrations in the kidney and brain and ATP concentrations in the kidney remained unchanged. The in-vivo P-glycoprotein function in these tissues was suppressed as evaluated by biliary and renal secretory clearances and brain distribution of rhodamine 123, a P-glycoprotein substrate. These findings suggest that factors other than P-glycoprotein concentration are involved in the systemic suppression of P-glycoprotein function in diseased rats. In Caco-2 cells, plasma collected from CCl4-treated rats exhibited a greater inhibitory effect on P-glycoprotein-mediated transport of rhodamine 123 than that from control rats, suggesting the accumulation of an endogenous P-glycoprotein substrate/inhibitor in the plasma of diseased rats. In fact, the plasma concentration of corticosterone, an endogenous P-glycoprotein substrate, increased 2-fold in CCl4-treated rats compared with control rats. It was demonstrated that P-glycoprotein function is systemically suppressed in rats with CCl4-induced acute hepatic failure, not only in the target organ (liver), but also in other organs (kidney and brain), although the P-glycoprotein concentration remained unchanged in the kidney and brain, and increased in the liver. In the systemic suppression of the P-glycoprotein function in the diseased state, the alteration of plasma concentrations or components of endogenous P-glycoprotein-related compounds, such as corticosterone, would likely be involved.
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PMID:Expression and function of P-glycoprotein in rats with carbon tetrachloride-induced acute hepatic failure. 1142 64

The effect of intracisternal injection of urocortin, an endogenous ligand for corticotropin-releasing factor (CRF) 2 receptor, on carbon tetrachloride (CCl4)-induced acute liver injury was investigated in rats. Intracisternal injection of urocortin dose-dependently enhanced elevation of serum alanine aminotransferase and aspartate aminotransferase levels induced by CCl4. Intracisternal urocortin also aggravated CCl4-induced histological changes of the liver. The aggravating effect of central urocortin on CCl4-induced acute liver injury was abolished by chemical sympathectomy, but not by vagotomy. These data demonstrate that urocortin acts in the brain to exacerbate acute liver injury through the sympathetic nervous system and suggest a possible involvement of the CRF2 receptor in the central CRF-induced exacerbation of acute liver injury in rats.
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PMID:Effect of central urocortin on carbon tetrachloride-induced acute liver injury in rats. 1168 49


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