Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetracera loureiri is one of the most valued herbs in Thai traditional medicine. In this study, we describe its in vitro and in vivo antioxidant and hepatoprotective activities. The ethanol extract of T. loureiri possessed potent antioxidant and strong free radical scavenging properties assayed using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH), respectively. The cytoprotective effects of T. loureiri were demonstrated in ethanolic extracts of freshly isolated rat hepatocytes against the chemical toxicants paracetamol and tertiary-butylhydroperoxide. The cells pretreated with the extract maintained the GSH/GSSG ratio and suppressed lipid peroxidation in a dose dependent manner. Pretreating rats with the ethanol extract orally, one hour prior to intraperitoneal injection of toxic doses of paracetamol, significantly prevented elevations of plasma ALT and AST. These results suggest that T. loureiri may be of potential therapeutic value in some liver disorders.
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PMID:Hepatoprotective and antioxidant activities of Tetracera loureiri. 1291 65

Acetaminophen (AAP) overdose causes formation of peroxynitrite in centrilobular hepatocytes. Treatment with glutathione (GSH) after AAP accelerated recovery of mitochondrial GSH levels, which scavenged peroxynitrite and protected against liver injury at 6 h. The objective of this investigation was to evaluate whether GSH treatment has a long-term protective effect against AAP-induced injury and whether it promotes liver regeneration. AAP (300 mg/kg) induced severe centrilobular necrosis and increased plasma alanine aminotransferase (ALT) activities (24 h: 3680 +/- 320 U/liter) in fasted C3Heb/FeJ mice. Only 53% of the animals survived for 24 h. Hepatic glutathione levels were still suppressed by 62% at 24 h compared with untreated controls (19.7 +/- 2.6 micromol/g). Glutathione disulfide (GSSG) concentrations were elevated by 455% compared with controls (74 +/- 3 nmol/g liver). Treatment with GSH at 1.5 h after AAP treatment attenuated liver necrosis and plasma ALT activities by 62 to 66% at 24 h. All animals survived up to 7 days. The hepatic GSH content recovered to control values; however, the GSSG levels were still elevated at 48 h (252 +/- 26 nmol/g). Expression of proliferating cell nuclear antigen (PCNA) and cell cycle proteins cyclin D1 and p21 were not detectable in controls or after AAP alone. Treatment with GSH after AAP induced expression of cyclin D1, p21, and PCNA (12-48 h). Thus, GSH treatment after AAP provided long-term hepatoprotection and promotes progression of cell cycle activation in hepatocytes.
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PMID:Scavenging peroxynitrite with glutathione promotes regeneration and enhances survival during acetaminophen-induced liver injury in mice. 1295 12

The response of fatty liver to stress conditions (t-butyl hydroperoxide [t-BH] or 36 h of fasting) was investigated by assessing intracellular glutathione (GSH) compartmentation and redox status, GSH peroxidase (GSH-Px) and reductase (GSSG-Rx) activities, lipid peroxidation (TBARs) and serum ALT levels in rats on a choline-deficient diet. Baseline cytosolic GSH was similar between fatty and normal livers, while the mitochondrial GSH content was significantly lower in fatty livers. With the except of cytosolic GSH-Px activity, steatosis was associated with significantly higher GSH-related enzymes activities. Liver TBARs and serum ALT levels were also higher. Administration of t-BH significantly decreased the concentration of cytosolic GSH, increased GSSG levels in all the compartments, and increased TBARs levels in cytosol and mitochondria and serum ALT; all these alterations were more marked in rats with fatty liver. Fasting decreased the concentration of GSH in all the compartments both in normal and fatty livers, increased GSSG, TBARs and ALT levels, and decreased by 50% the activities of GSH-related enzymes. Administration of diethylmaleimide (DEM) resulted in cytosolic and microsomal GSH pool depletion. Administration of t-BH to DEM-treated rats further affected cytosolic GSH and enhanced ALT levels, whereas the application of fasting to GSH depleted rats mainly altered the mitochondrial GSH system, especially in fatty livers. This study shows that fatty livers have a weak compensation of hepatic GSH regulation, which fails under stress conditions, thus increasing the fatty liver's susceptibility to oxidative damage. Differences emerge among subcellular compartments which point to differential adaptation of these organelles to fatty degeneration.
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PMID:Adaptation of subcellular glutathione detoxification system to stress conditions in choline-deficient diet induced rat fatty liver. 1501 60

Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and we have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL + BBS (10 microg/kg, s.c. x3), BDL + NT (300 microg/kg, i.p.). At the end of the experiment, on day 10, serum total bilirubin and alanine aminotransferase (ALT) levels were determined and endotoxin was measured in portal and aortic blood. Liver tissue samples were examined histologically for evaluation of the ratio of portal tracts presenting changes of obstructive cholangiopathy and neutrophils' number in portal tracts. In addition, hepatic oxidative status was estimated on liver homogenates by measurements of lipid peroxidation (malondialdehyde), protein oxidation (protein carbonyl groups) and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulfides (NPSSR) and protein thiols (PSH)]. Administration of BBS or NT significantly reduced portal and aortic endotoxaemia observed in obstructive jaundice. Both agents significantly ameliorated liver injury, as demonstrated by improvement of obstructive cholangiopathy and reduction of ALT. This effect was accompanied by prevention of lipid peroxidation, protein oxidation and decrease of the oxidized forms GSSG and NPSSR. Moreover, neutrophil accumulation in portal tracts was significantly decreased. In conclusion, this study shows that gut regulatory peptides BBS and NT reduce cholestatic liver injury, exerting protective effects on portal tract architecture, neutrophil infiltration and hepatic oxidative stress in bile duct ligated rats.
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PMID:Gut regulatory peptides bombesin and neurotensin reduce hepatic oxidative stress and histological alterations in bile duct ligated rats. 1517 37

The reticulocytes and the ageing red blood cells (RBCs) namely young (Y), middle-aged (M) and old RBCs (O) of female Wistar rats from different groups such as control animals (C), controls treated with vanadate (C + V), alloxan-induced diabetic (D), diabetic-treated with insulin (D + I) and vanadate (D + V), were fractionated on a percoll/BSA gradient. The following enzymes were measured - hexokinase (HK), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione-s-transferase (GST), alanine aminotransferase (AlaAT), aspartate aminotransferase (AsAT) and arginase in the hemolysates of all the RBCs fractions. Decreases in the activity of HK and AsAT by about 70%, arginase and GSH-Px by 30% in old RBCs were observed in comparison to reticulocytes of control animals. Increases in the activity of GSSG-R by 86%, AlaAT by more than 400% and GST by 70% were observed in old RBCs in comparison to reticulocytes of control animals. Alloxan diabetic animals showed a further decrease in the activities of HK in Y RBCs by 37%, M RBCs by 39% and O RBCs by 32%, GSH-Px activity in Y RBCs by 13%, M RBCs by 20% and O RBCs by 33% and GST activity in Y RBCs by 14%, M RBCs by 42% and O RBCs by 60% in comparison to their corresponding cells of control animals. An increase in the activity of all the enzymes studied was also observed in reticulocytes of diabetic animals in comparison to reticulocytes of controls. The GSSG-R activity was found to be increased in Y RBCs by 49%, M RBCs by 67% and O RBCs by 64% as compared to the corresponding age-matched cells of control animals. The activity of arginase also decreased in Y RBCs by about10%, M RBCs by 20% and O RBCs by 30% in comparison to the age-matched cells of control animals. A decrease in the activity of AsAT in Y and M RBCs by 30%, and O RBCs by 25% was observed in diabetic animals in comparison to the age-matched cells of control animals. The activity of AlaAT was found to be decreased by more than 10% in Y and M RBCs and 25% in O RBCs of diabetic animals in comparison to the age-matched cells of control animals. Insulin administration to diabetic animals reversed the altered enzyme activity to control values. Vanadate treatment also reversed the enzyme levels except for that of GST in old cells.
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PMID:Protective effects of sodium orthovanadate in diabetic reticulocytes and ageing red blood cells of Wistar rats. 1528 6

For more than 40 years coumarin has been successfully used in the therapy of chronic venous insufficiency (CVI). The occurrence of liver injuries is rather rare and happens predominantly when doses are administered which are significantly higher than necessary for therapeutical use. Such effects caused by high coumarin concentrations are reproducible in in vivo experiments in mice or rats and HepG2-cells. In order to characterize the mechanism of liver injuries, the isolated perfused rat liver has been chosen as model. Since liver injuries are quite rare, if coumarin is used in co-medication with troxerutin, a possible protective influence of this flavonoid has been investigated. In concentrations higher than 4 mmol/l, coumarin alone is effective in the isolated perfused rat liver. Then the release of the enzymes alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increases and there is a measurable reduction of perfusion flow, oxygen consumption and rate of bile secretion. Additionally, the concentrations of hepatic adenosine triphosphate (ATP) and oxidized and total glutathione (GSSG/GSH) decrease. In the livers of fasting animals, coumarin doubles the concentration of hepatic malondialdehyde (MDA). This effect cannot be detected if troxerutin is added. In general, troxerutin reduces the concentration of all coumarin-metabolites in the perfusate and bile and changes the ratio of the main metabolites, coumarin: 3-hydroxycoumarin: 7-hydroxycoumarin. An analysis of the metabolic steps also shows that the amount of coumarin eliminated via faeces does not stem from absorbed coumarin, because the amount of orally applied coumarin detectable in the bile is less than 1%. The study demonstrates that troxerutin has hepatoprotective properties and thus protects the liver from a possible lipid peroxidation caused by coumarin. However, it is necessary to point out that these adverse effects caused by coumarin can be detected only in very high concentrations considerably above the regular therapeutical dosage. This allows the conclusion that troxerutin is a beneficial cofactor in coumarin preparations used for the therapy of chronic venous insufficiency.
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PMID:Troxerutin protects the isolated perfused rat liver from a possible lipid peroxidation by coumarin. 1569 8

Concomitant oral supplementation of Aloe vera, (1, 2 or 5% w[sol ]v in drinking water) during arsenic exposure (0.2 mg[sol ]kg, intraperitoneally, once daily for 3 weeks) was investigated in rats for its protective value. Animals exposed to arsenic (III) showed a significant inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity, a marginal decrease in glutathione (GSH) and an increase in zinc protoporphyrin (ZPP) level in blood. White blood corpuscles (WBC) level decreased while most of the other clinical blood parameters like red blood cells count, haemoglobin, MCV, MCH, MCHC ratio and platelet number, etc. remained unaltered on arsenic exposure. Hepatic reduced GSH, oxidized glutathione (GSSG) level remained unaltered, thiobarbituric acid reactive substance (TBARS) level increased significantly while the activity of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and catalase decreased on arsenic exposure. Renal GSH contents decreased while superoxide dismutase (SOD) activity decreased significantly on arsenic exposure. Concomitant administration of Aloe vera had remarkable protective action on inhibited blood ALAD activity and restored blood GSH level while most of the other blood biochemical parameters remained unchanged on Aloe vera supplementation. Interestingly, most of hepatic biochemical variables indicative of oxidative stress showed protection; no effect of Aloe vera on blood and liver arsenic concentration was noted. Also, no effect of Aloe vera on most of the altered renal biochemical parameters were noticed. The results thus lead us to conclude that simultaneous supplementation of Aloe vera protects against arsenic induced oxidative stress but does not influence the arsenic concentration in these organs.
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PMID:Protective value of Aloe vera against some toxic effects of arsenic in rats. 1579 4

The aim of this paper is to assess the antioxidant properties of rat liver in the course of acute and chronic fasciolosis. Wistar rats were infected per os with 30 metacercariae of Fasciola hepatica. Liver activities of antioxidant enzymes and concentrations of non-enzymatic antioxidants were determined at 4, 7, and 10 weeks post-infection. Activities of superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) were decreased, catalase (CAT) activity was increased and non-enzymatic antioxidant concentrations (reduced glutathione, vitamins C, E and A) were reduced simultaneously with enhancement of lipid peroxidation processes as evidenced by increased levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Changes in the antioxidant abilities of the liver and in the phospholipid structure of the cell membrane were accompanied by rising activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as markers of liver damage.
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PMID:Antioxidant potential of rat liver in experimental infection with Fasciola hepatica. 1592 4

Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response.
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PMID:Endogenous antioxidant defence system in rat liver following mercury chloride oral intoxication. 1597 96

3-Butene-1,2-diol (BDD), an allylic alcohol and major metabolite of 1,3-butadiene, has previously been shown to cause hepatotoxicity and hypoglycemia in male Sprague-Dawley rats, but the mechanisms of toxicity were unclear. In this study, rats were administered BDD (250 mg/kg) or saline, ip, and serum insulin levels, hepatic lactate levels, and hepatic cellular and mitochondrial GSH, GSSG, ATP, and ADP levels were measured 1 or 4 h after treatment. The results show that serum insulin levels were not causing the hypoglycemia and that the hypoglycemia was not caused by an enhancement of the metabolism of pyruvate to lactate because hepatic lactate levels were either similar (1 h) or lower (4 h) than controls. However, both hepatic cellular and mitochondrial GSH and GSSG levels were severely depleted 1 and 4 h after treatment and the mitochondrial ATP/ADP ratio was also lowered 4 h after treatment relative to controls. Because these results suggested a role for hepatic cellular and mitochondrial GSH in BDD toxicity, additional rats were administered N-acetyl-l-cysteine (NAC; 200 mg/kg) 15 min after BDD administration. NAC treatment partially prevented depletion of hepatic cellular and mitochondrial GSH and preserved the mitochondrial ATP/ADP ratio. NAC also prevented the severe depletion of serum glucose concentration and the elevation of serum alanine aminotransferase activity after BDD treatment without affecting the plasma concentration of BDD. Thus, depletion of hepatic cellular and mitochondrial GSH followed by the decrease in the mitochondrial ATP/ADP ratio was likely contributing to the mechanisms of hepatotoxicity and hypoglycemia in the rat.
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PMID:Protection of rats against 3-butene-1,2-diol-induced hepatotoxicity and hypoglycemia by N-acetyl-l-cysteine. 1612 19


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