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)

The hypothetical involvement of hydrogen peroxide (H2O2) in carbon tetrachloride (CCl4)-induced acute liver injury and the potential preventive effect of catalase on hepatotoxicity have been studied in acatalasemic (C3H/AnLCsbC2b) mice and compared with normal (C3H/AnLCsaCsa) mice. A single intraperitoneal injection of CCl4 (20% in olive oil/g body weight) caused increases in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in both mouse groups, but the extents of increases did not show significant differences between the two mouse groups until 12 h. The variation in increases of serum AST and ALT levels in acatalasemic and normal mice turned to be distinctly different from 12 h. At 18 h (peak point for ALT) and 24 h (peak point for AST), the serum enzyme levels in acatalasemic mice were nearly two-fold higher than those in normal ones, the difference being statistically significant (p < 0.01). The liver malondialdehyde (MDA) level in acatalasemic mice was also higher than that in normals at 18 h (p < 0.05). The extent of the centrilobular necrosis was histologically more severe in acatalasemic mice. The catalase activity in livers of acatalasemic mice was one-third to one-fifth those of normal mice (p < 0.05) before and after treatment. The decreased catalase activity in acatalasemic mice might increase tissue or cellular levels of H2O2 during the later phase of the acute liver injury. From these findings, we conclude that H2O2 breakdown in liver would account for the difference in the later stages of the acute liver damage between the two groups of mice, and catalase is important in inhibiting hepatotoxicity of CCl4 in the later stage.
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PMID:Enhanced liver injury in acatalasemic mice following exposure to carbon tetrachloride. 882 76

We found that NADPH-dependent ubiquinone reductase (NADPH-UQ reductase) in rat liver cytosol reduces ubiquinone (UQ) to ubiquinol (UQH2) in lipid membranes and consequently inhibits lipid peroxidation [Takahashi T., et al., Biochem. J., 309, 883-890 (1995)]. Here we examined whether or not this UQH2-regenerating system functions as a cellular antioxidant defense in animals. Rats were given UQ-10 for 2 weeks, and were then exposed to carbon tetrachloride (CCl4). The UQ-10 supplement increased only in the NADPH-UQ reductase and the UQH2-10 pool of rat liver without any appreciable change in the levels of other antioxidant factors. On the other hand, CCl4 markedly increased plasma aspartate aminotransferase and alanine aminotransferase, liver weight and thiobarbituric acid reacting substances formation, which are indicators of CCl4-hepatitis, and it decreased the liver levels of L-ascorbic acid, reduced form of glutathione (GSH), alpha-tocopherol, NADPH-UQ reductase and glutathione S-transferase. However, all the above indicators of CCl4-induced hepatitis were significantly improved in rats given UQ-10. Furthermore, alpha-tocopherol, but neither L-ascorbic acid nor GSH, was significantly saved. UQ-10 supplement also was recovered glutathione S-transferase and NADPH-UQ reductase activities slightly. These results indicated that UQ-10 given to rats increased the cellular UQH2-10 pool and cytosolic NADPH-UQ reductase activity in their livers, resulting in the inhibition of lipid peroxidation in the biomembranes, and consequently protected the rats from the CCl4-hepatotoxicity.
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PMID:Cellular antioxidant defense by a ubiquinol-regenerating system coupled with cytosolic NADPH-dependent ubiquinone reductase: protective effect against carbon tetrachloride-induced hepatotoxicity in the rat. 887 5

Seven female, 2-year-old, nonpregnant, Merino ewes were treated with a nonlethal dose of 0.3 ml/kg body mass carbon tetrachloride (CCl4) in 1:1 v/v dilution with paraffin oil via a stomach tube into the rumen. Blood samples were collected one day before and on the first, second, third, seventh and tenth day after toxin exposure to study the changes of the lipid peroxidation (LP) status of red blood cell haemolyzate (RBC-haem). The severity of liver damage was monitored by determination of aspartate aminotransferase (AST) activity and bilirubin concentration in the blood plasma. Twenty-four h after CCl4 exposure all animals became lethargic and anorexic, their heart rate and respiratory rate increased. On the subsequent two days these signs became more severe, but by the 10th day the symptoms disappeared. On the 1st and 2nd day following CCl4 exposure the concentration of malondialdehyde (MDA)--an end product of LP--in RBC-haem significantly increased. A slight decrease was found on the 3rd, 7th and 10th day, but MDA values remained significantly higher than the basal ones. The activity of glutathione peroxidase (GPX) in RBC-haem increased slowly on the 1st and 2nd day, then it rose intensively on the third day. GPX activity remained elevated until the 7th day, but on the 10th day it dropped again. Catalase (Cat) activity in RBC-haem did not show any significant changes during the experiment. AST activity in blood plasma showed a two-fold increase in the first three days; later on the high values decreased. Total and direct plasma bilirubin concentration slightly increased on the 3rd day, then both decreased. LP effects in CCl4-induced hepatocellular injury were significant in sheep, in line with the results of experiments on other species such as rats. The LP effects were demonstrated by the elevated MDA concentration and GPX activity.
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PMID:Evaluation of blood lipid peroxidation parameters in carbon tetrachloride (CCl4) toxicity in sheep. 888 40

Cytochrome P450 2E1 (P450 2E1) is active in both the detoxification and activation of small organic molecules. The effects of 2-(allylthio)pyrazine (2-AP) on P450 2E1-catalytic activity and the expression of rat hepatic P450 2E1 were examined. 2-AP competitively inhibited 4-nitrophenol hydroxylase activity in vitro (Ki, 12 microM). 2-AP treatment of rats (200 mg/kg/day, p.o., 1-3 days old) resulted in 20-30% decreases in the rates of P450 2E1-specific metabolic activities. Immunoblot analysis also revealed that hepatic microsomes isolated from 2-AP-treated rats showed substantial decreases in P450 2E1 level. 2-AP-suppressed isoniazid (INH)-inducible hepatic P450 2E1 levels, as shown by both metabolic activities and immunoblot analyses. Thus, 2-AP was effective in suppressing both constitutive and inducible P450 2E1 expression. Northern blot analysis showed that 2-AP transiently suppressed the hepatic P450 2E1 mRNA level, suggesting that suppression in P450 2E1 expression by 2-AP may be mediated in part by transcriptional inactivation. Hepatoprotective effects of 2-AP against toxicants were monitored in mice. 2-AP pretreatment prior to the administration of lethal doses of acetaminophen (AAP) or INH substantially reduced toxicant-induced mortality. Whereas serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were markedly elevated after AAP administration (i.e. 9-20-fold), 2-AP pretreatment of animals before AAP administration resulted in >95% decreases in elevated serum aminotransferase activities. 2-AP was also effective against CCl4-induced hepatotoxicity. Whereas CCl4 treatment caused 35-70-fold increases in aminotransferase activities, treatment of mice with 2-AP (>10 mg/kg) resulted in the blocking of CCl4-induced liver toxicity. The hepatoprotective effect of 2-AP was in part due to 2-AP-induced elevation of hepatic GSH levels. Whereas AAP or CCl4 treatment resulted in 70-80% reduction in hepatic GSH levels, pretreatment of mice with 2-AP caused a 40-210% elevation in hepatic GSH levels, as compared with either AAP or CCl4 alone. 2-AP pretreatment also reduced AAP- or CCl4-induced increases in lipid peroxidation in a dose-dependent manner. The results of these metabolic activities and of immunoblot and RNA blot analyses demonstrate that 2-AP is efficacious in suppressing constitutive and inducible P450 2E1 expression and effective in protecting against toxicant-induced liver toxicity.
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PMID:Inhibition of cytochrome P450 2E1 expression by 2-(allylthio)pyrazine, a potential chemoprotective agent: hepatoprotective effects. 906 29

1. The use of the cytoplasmic enzyme, alpha glutathione s-transferase (alpha-GST) as an early index of carbon tetrachloride (CCl4) toxicity in the rat was investigated and compared with a standard enzyme, marker, aspartate aminotransferase (AST). The hepatotoxic effects of CCl4 in the rat were determined in a time and dose-response study. 2. Following CCl4 exposure, alpha-GST release was shown to be an earlier and more sensitive biomarker of hepatotoxicity than AST. 3. Significant increases in alpha-GST were detected 2 h after CCl4 exposure. Using the enzyme marker AST, this early hepatotoxic injury went undetected. At 6 and 16 h, alpha-GST was also a more sensitive indicator of hepatotoxicity than AST. 4. alpha-GST release was significantly increased at a dose of 5 microliters/kg, the lowest concentration of CCl4 administered and clearly responded in a dose-dependent manner with increasing doses of CCl4. In contrast, release of AST did not reach statistical significance until a dose of 25 microliters/kg. 5. Thus, these findings indicate that alpha-GST is a more sensitive and more accurate reflector of CCl4 induced hepatotoxicity than AST.
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PMID:Alpha-glutathione s-transferase (alpha-GST) release, an early indicator of carbon tetrachloride hepatotoxicity in the rat. 908 68

The hepatoprotective effect of various fractions (n-hexane, CHCl3, EtOAc, n-BuOH, and H2O) of Ban-zhi-lian derived from Scutellaria rivularis Benth was studied against carbon tetrachloride (CCl4), D-galactosamine (D-GalN) and acetaminophen (APAP)-induced acute hepatotoxicity in rats. Liver damage was assessed by quantifying serum activities of glutamate oxaloacetate transaminase (sGOT) and glutamate pyruvate transaminase (sGPT), as well as by histopathological examination. The results indicated that the CHCl3 fraction and EtOAc fractions exhibited the greatest hepatoprotective effects on CCl4-induced liver injuries, the CHCl3 fraction and n-hexane fraction are most potent against D-GalN-induced intoxication, and the CHCl3 fraction represented the most liver-protective effect on APAP-induced hepatotoxicity. The pathological changes of hepatic lesions caused by these three hepatotoxicants were improved by treatment with the fractions mentioned above, which were compared to Glycyrrhizin (GLZ) and Silymarin as standard reference medicines.
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PMID:Hepatoprotective effect of the fractions of Ban-zhi-lian on experimental liver injuries in rats. 920 8

Present work was undertaken to ascertain the hepatoprotective effect of Swertia chirata in albino rats. Intraperitoneal injection of CCl4 (1 ml/kg body wt on every 72 hr. for 16 days) significantly increased serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and alkaline phosphatase (ALP) activities and bilirubin level in rat, but liver glycogen and serum cholesterol levels were decreased. Histologically it produced hepatocytic necrosis especially in the centrilobular region. Simultaneous treatments with S. Chirata (in different doses, viz, 20, 50 and 100 mg/kg body wt daily) and CCl4 (similar dose to that mentioned earlier) caused improvement at both biochemical and histopathological parameters compared to that of CCl4 treatment alone but it was most effective when S. chirata was administered in a moderate dose (50 mg/kg body wt).
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PMID:Hepatoprotective effect of Swertia chirata on rat. 931 40

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

The relationships between the pharmacokinetic behaviour of glycyrrhizin and its restorative effect for hepatic function were investigated in patients with chronic hepatitis and in rats chronically treated with carbon tetrachloride (CCl4-treated rats). In patients, the restorative effects in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were 62.2 +/- 7.4 and 64.4 +/- 7.5%, respectively, after daily 80 mg intravenous (i.v.) doses of glycyrrhizin for 2 weeks, and 63.1 +/- 19.1 and 68.7 +/- 15.2% after 120 mg doses. The present work suggests that the threshold plasma glycyrrhizin concentration for sufficient effect is near 5 micrograms mL-1. In rats, the total body clearance (Cltot) for glycrrhizin in the CCl4-treated rats after i.v. administration of glycyrrhizin (5 mg kg-1 dose) was three-tenths of that of the control, and the t1/2 for glycyrrhizin was 3.4-fold longer than that of the control. A good correlation was observed between Cltot and AST (r = -0.838) or ALT (r = -0.873) activity in both rats. When glycyrrhizin was administered intraperitoneally (i.p.) three times a week for 2 weeks, both the AST and ALT activities in the CCl4-treated rats showed a greater improvement than for a 10 mg kg-1 dose. Furthermore, the finding on the threshold plasma concentration in patients as above was also supported from the results of the experiments in rats.
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PMID:The pharmacokinetics of glycyrrhizin and its restorative effect on hepatic function in patients with chronic hepatitis and in chronically carbon-tetrachloride-intoxicated rats. 937 28

The aim of this study was to evaluate the tolerance of normothermic liver ischemia with different degrees of hepatic function in cirrhotic rats. Liver cirrhosis was induced by administering carbon tetrachloride (CCl4) in water solution to male Wistar rats. Hepatic function was graded using the plasma levels of antithrombin III, albumin, and bilirubin and the presence of ascites. Rats were distributed in four groups: noncirrhotic (control group), compensated cirrhosis (group A), decompensated cirrhosis (group B), and decompensated cirrhosis with ascites (group C). Groups A, B, and C were significantly different in all four parameters studied (P < .003). Subtotal liver ischemia was performed for periods of 0, 30, 45, 60, and 75 minutes. At the end of the procedure, the nonischemic lobes were resected. Postoperative evolution of alanine aminotransferase, aspartate aminotransferase, and bilirubin levels was also recorded. Survival rates after the same periods of ischemia were statistically different (P < .05): control group, 7 of 7 after 45 minutes (100%), 7 of 7 after 60 minutes (100%), and 4 of 9 after 75 minutes (44%); group A, 7 of 7 after 45 minutes (100%) and 1 of 7 after 60 minutes (14%); group B, 7 of 7 after 0 minutes (100%), 5 of 7 after 30 minutes (71%), and 1 of 7 after 45 minutes (14%); and group C, 0 of 5 after 0 minutes (0%) and 1 of 7 after 30 minutes (14%). No differences were found in the postoperative course of transaminases. However, bilirubin levels found 24 hours and 7 days after ischemia were significantly greater in cirrhotic rats, and this was directly related to the degree of hepatic insufficiency (P < .001). Histological examination of the livers exposed to CCl4 showed features of liver cirrhosis with ductal proliferation. The ischemia time tolerated by cirrhotic rat livers is shorter than the time tolerated by normal rats. Tolerance to hilar vascular occlusion depends on the degree of hepatic insufficiency. Rats with decompensated cirrhosis and ascites do not tolerate any surgical procedure.
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PMID:Vascular occlusion in hepatic resections in cirrhotic rat livers: an experimental study in rats. 940 63


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