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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholestasis, or impaired bile flow, occurs in a wide variety of liver diseases and causes hepatic damage by retention and accumulation of toxic hydrophobic bile salts inducing persistent inflammation and oxidative stress. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and anti-inflammatory agent against autoimmune disease, on hepatic damage produced by double ligature of the extrahepatic biliary duct in Wistar Albino rats. Cholestasis was done by double ligature and section of the extrahepatic biliary duct (BDL). Leflunomide was given i.g. 10 mg/kg/day. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and levels of direct bilirubin. Malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO), catalase (CAT) and superoxide dismutase (SOD) were determined to the oxidative status in the liver tissue. Myeloperoxidase (MPO) activity and levels of tissue hydroxyproline (HPR) were determined to neutrophil activation and collagen accumulation, respectively. Further, histological changes were studied. Treatment with leflunomide markedly reduced serum transaminase activities as compared to BDL rats. At the same time leflunomide significantly inhibited increases in liver MDA, PC and NO levels and also attenuated the depletion of CAT and SOD in the liver after bile duct ligation. Similarly, increase in tissue MPO activity and HPR due to BDL was also attenuated by leflunomide treatment. These findings were supported by histopathological findings. These findings suggested that leflunomide can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress and inflammatory process.
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PMID:Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment. 1689 9

Stellate cells are activated by free radicals, and synthesize collagen. N-acetylcysteine (NAC) is a precursor of reduced glutathione and a potent scavenger of hydroxyl radicals and has potential antifibrotic effects. We aimed to test the effects of NAC on bile duct ligation (BDL) induced liver damage in rats. Forty-seven Wistar rats were divided into 5 groups: group 1, BDL+NAC (n=10); group 2, BDL (n=10); group 3, sham+NAC (n=10); group 4, sham (n=10); and group 5, control group (n=10). NAC (50 micromol/kg per day) or saline of single doses were administered intraperitoneally for 28 days. Serum biochemical and liver oxidative stress parameters were studied. Liver collagen level was determined by the method of Lopez de Leon and Rojkind. Liver slides were stained by hematoxylin and eosin and Masson trichrome\Gomory reticulum staining. Aspartate aminotransferase (AST) and alkaline phosphatase levels in the BDL+NAC group were lower than the BDL group and were higher than the control groups (all P< .001). Malondialdehyde, luminal, and glutathione levels in group 1 were lower than the BDL group (P= .01, P= .002, and P< .001) and higher than the control groups (all P< .001). NAC had no effect on alanine aminotransferase (ALT), gammaglutamyl transferase, bilirubin, albumin, or lucigenin levels. Liver collagen levels were higher in the BDL groups (P< .001); however, NAC had no effect on the collagen levels. The BDL groups showed stage 3 fibrosis; all the control groups were normal. NAC improved some biochemical parameters (AST, alkaline phosphatase) and oxidative stress parameters (malondialdehyde, luminol, glutathione) in the BDL model. NAC was found to be effective on cholestasis-induced hepatotoxicity. However, NAC was inefficient as an antifibrotic agent within a 1-month period of administration in the BDL model.
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PMID:The effects of N-acetylcysteine on bile duct ligation-induced liver fibrosis in rats. 1743 97

The aim of this study was the evaluation of the hepatic damages following a subchronic exposure to malathion, an organophosphorus (OP) insecticide. Malathion was administered intragastrically in 1 ml corn oil containing 100 mg/kg Body Weight daily for 32 days. Malondialdehyde (MDA) concentration superoxide dismutase (SOD) and catalase (CAT) activities were analysed using a non-denaturing electrophoresis. The serum activities of Pseudocholinesterase (PchE), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were determined. Malathion exposure leads to a significant decrease in AchE activity, an increase in hepatic MDA, and in serum ASAT and ALAT activities. A positive correlation between serum transaminases levels and hepatic MDA was demonstrated. These results indicate that malathion exposure induced lipid peroxidation LPO, a process of degradation of membrane lipids, involving the deterioration of the cellular integrity. We have recorded a slight increase in antioxidant enzymes activities. This leads us to suggest an insufficient elimination of free radicals, causing cytotoxic effects.
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PMID:Biochemical evaluation of hepatic damage in subchronic exposure to malathion in rats: effect on superoxide dismutase and catalase activities using native PAGE. 1872 84

Recent studies have documented that remote organs are affected by ischemic injury to the kidney. Here we studied whether the liver also suffers damage during induction of renal ischemia-reperfusion in rats and compared this to bilateral nephrectomy. Hepatic levels of tumor necrosis factor-alpha increased significantly after 6 and 24 h of renal ischemia or nephrectomy. Malondialdehyde, an index of lipid peroxidation, increased while total glutathione was decreased in the liver in both the renal ischemia and nephrectomy groups, suggesting activation of oxidative stress. Expression of liver spermine-spermidine acetyl transferase, an enzyme upregulated in early phases of hepatic injury was significantly increased 6 h after either kidney ischemia or nephrectomy. Apoptosis was increased in hepatocytes 24 h after nephrectomy. We also found histological evidence of hepatocyte injury following both ischemia and bilateral nephrectomy. Infusion of reduced glutathione, before the induction of renal ischemia, significantly improved liver architecture and was associated with a reduction in hepatic malondialdehyde and serum alanine transaminase levels. Our study shows that acute kidney ischemia or renal failure activates oxidative stress and promotes inflammation, apoptosis, and tissue damage in hepatocytes.
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PMID:Ischemic and non-ischemic acute kidney injury cause hepatic damage. 1917 57

The aim of this study was to evaluate the effects of methylene blue against cholestatic oxidative stress and liver damage after ligation of the common bile duct in male Wistar rats. Eight animals were included in each of the following five groups: untreated control, methylene blue control, sham-operated, bile-duct ligation, and bile-duct ligation plus methylene blue. Methylene blue was administered intraperitoneally for 14 days at a daily dose of 2mg/kg per day. All rats were sacrificed 2 weeks following the experimental treatment and the livers of all groups were examined biochemically and histopathologically. The severity of cholestasis and hepatic injury were determined by changes in the plasma, including enzymatic activities: aspartate aminotransferase, alanine aminotransferase, gamma glutamine transferase, and also bilirubin levels. Malondialdehyde, nitric oxide and superoxide dismutase were measured to indicate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined as measures of neutrophil activation and collagen accumulation, respectively. Liver damage was significantly prevented in the bile-duct ligated rats treated with methylene blue compared with the control bile-duct ligated rats without methylene blue. Treatment with methylene blue markedly reduced activities of serum transaminase, gamma glutamine transferase and bilirubin levels as compared to bile-duct ligated rats without methylene blue. Positive immunolabelling for alpha-smooth muscle actin (alpha-SMA) was increased, especially in vascular smooth muscle cells, fibrotic septa and also around the proliferated bile ducts, after bile-duct ligation. Only weak alpha-SMA immunolabelling was seen in livers of rats treated with methylene blue. These results indicate that methylene blue can attenuate hepatic damage in extrahepatic cholestasis by reducing oxidative stress and inflammatory processes.
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PMID:Effects of methylene blue in reducing cholestatic oxidative stress and hepatic damage after bile-duct ligation in rats. 1921 52

Burns cause thermal injury to local tissue, trigger systemic inflammatory processes and activate lipid peroxidation, leading to multiple distant organ injury. Melatonin is a lipid- and water-soluble antioxidant and membrane stabilizer with antiinflammatory, hepatoprotective and gastroptotective properties, among others. We studied the influence of melatonin on hepatic damage induced by thermal skin injury and its possible relation to hepatic lipid peroxidative status and systemic inflammatory response. Under ether anesthesia the shaved dorsum of rats was exposed to a 90 degrees C bath for 10 s. Melatonin was administered intraperitoneally immediately after burns. Malondialdehyde (MDA), aspartate transaminase (AST) and alanine transaminase (ALT) were determined in liver and blood plasma and used as markers of oxidative status. Plasma C-reactive protein (CRP) was used as a marker of systemic inflammatory response. Thermal skin injury caused significant elevation of hepatic MDA by 48%, plasma CRP levels by 30% and plasma AST and ALT activities by 2- and 3.5-fold, respectively, in comparison with normal control rats. Treatment with melatonin (10 mg/kg) significantly inhibited the elevation in hepatic MDA and plasma CRP levels, reaching control values at 24 h. Melatonin treatment restricts the elevation of plasma AST and ALT activities (P < 0.001), which remain significantly increased as compared with controls. In conclusion, the protective effect of melatonin is likely to be due to attenuated lipid peroxidation and interference with reduced oxidative stress and inflammatory response, as evidenced by decreased hepatic MDA and plasma CRP levels.
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PMID:Protective effect of melatonin against oxidative hepatic injury after experimental thermal trauma. 1935 93

The goal of this study was to evaluate the possible protective effects of sphingosylphosphorylcholine (SPC) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. Fifty-six animals were included in each of the following 7 groups: control, SPC control, phosphate-buffered solution control, sham operated, bile duct ligation (BDL), BDL plus phosphate-buffered solution, and BDL plus SPC. Sphingosylphosphorylcholine was administered 14 days at a daily dose of 2 microm/mL intraperitoneally. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of aspartate aminotransferase, alanine aminotransferase, gama glutamin transferase, and levels of total bilirubin and direct bilirubin. Malondialdehyde, nitric oxide, and superoxide dismutase were determined to evaluate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined to assess neutrophil activation and collagen accumulation, respectively. Treatment with SPC markedly reduced serum transaminase activities as compared to BDL rats. Sphingosylphosphorylcholine also inhibited the increase in liver malondialdehyde; nitric oxide levels significantly and also attenuated the depletion of superoxide dismutase in the liver after BDL. Similarly, the increase in tissue myeloperoxidase activity and hydroxyproline owing to BDL was also attenuated by the SPC treatment. These data were supported by histopathologic findings. The alpha-smooth muscle actin-positive cells in the BDL were observed to be reduced with the SPC treatment. In conclusion, these findings suggested that SPC can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress, and inflammatory process. All these findings suggest that SPC may be a promising new therapeutic agent for cholestatic liver injury.
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PMID:Effects of sphingosylphosphorylcholine against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. 1936 29

Ischemia and reperfusion (I/R) injury is characterized by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. This study was designed to assess the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (CysLT1), on hepatic I/R injury in rats. Wistar albino rats through clamping hepatic artery, portal vein, and bile duct, were subjected to 45 min of hepatic ischemia followed by 60 min reperfusion period. Montelukast (10 mg/kg; i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period, the rats were killed by decapitation. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and proinflammatory cytokines (TNF-alpha and IL-1beta) were determined in blood samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) and Na+, K+-ATPase activities were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. Serum ALT, AST, and LDH activities were elevated in the I/R group, while this increase was significantly decreased by montelukast treatment. Hepatic GSH levels and Na+, K+-ATPase activity, significantly depressed by I/R, were elevated back to control levels in montelukast-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels, and MPO activity due to I/R injury were reduced back to control levels with montelukast treatment. Since montelukast administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that montelukast with its anti-inflammatory and antioxidant properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.
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PMID:Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats. 1951 88

To investigate the effects of atorvastatin and cinnamon on serum lipid profile, oxidative stress, antioxidant capacity, hepatic enzymes activities, nitric oxide (NO) as well as homocysteine (Hcy) in hypercholesterolemic rats, 48 male albino rats, weighing 130-190 gm were divided into 2 groups, normal group fed on basal rat chow diet (n=12) and high cholesterol group (HCD) were fed on 1% cholesterol-enriched diet for 15 day (n=36). Hypercholesterolemic rats were divided into 3 subgroups (n=12 for each) fed the same diet and treated with atorvastatine (HCD+Atorvastatin) or cinnamon extract (HCD+cinnamon) or none treated (HCD) for 3&6 weeks. Serum triglycerides (TG), Total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), ALT, AST, NO, Hcy, hepatic reduced glutathione (GSH), Malondialdehyde (MDA) and antioxidant enzymes, Superoxide dismutase (SOD) and catalase activity were measured. Results showed that HCD increased significantly TG, TC, LDL-C, ALT, AST, Hcy and hepatic MDA, while lowered significantly antioxidant enzyme activities and NO levels. Atorvastatin therapy significantly increased HDL-C, NO and antioxidant activity while decreased LDL-C, MDA and Hcy concentrations. Serum TG, TC, LDL-C, ALT, AST and hepatic MDA levels were significantly lowered meanwhile, serum HDL, NO values and hepatic antioxidant activities were significantly, higher in cinnamon-treated than untreated group. These results indicate that lipid abnormalities, oxidative injury and hyperhomocystienemia were induced by HCD and this study recommend that administration of atorvastatine or cinnamon provided protection against the lipemic-oxidative disorder and act as hypocholesterolemic, hepatoprotective agent and improve cardiovascular function through modulation of oxidative stress, NO and Hcy.
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PMID:Oxidative markers, nitric oxide and homocysteine alteration in hypercholesterolimic rats: role of atorvastatine and cinnamon. 1991 18

Current studies evaluated the effect of acute and subacute exposure to chloroform (CHCl(3)) on rat liver and the implication of oxidative stress. For this purpose, different doses of CHCl(3) (150, 300 and 450 mg/kg bw) were administered intraperitoneally (ip) to male Wistar rats. Malondialdehyde (MDA), glutathione (GSH), reduced cytochrome c and metallothioneins (MTs) levels as well as the activities of catalase (CAT) and glutathione peroxidase (GPx) and the activities of the biochemical markers of hepatic injury (alanine transaminase [ALT] and aspartate transaminase [AST]) were determined. CHCl(3) did not cause a significant increase in hepatic lipid peroxidation. However, dose-dependant and/or time dependant effects of CHCl(3) were demonstrated on most of the oxidative stress parameters measured, namely the GSH depletion and the superoxide anion production. Acute exposure CHCl(3) increased the aminotransferase and GPx activities and reduced cytochrome c levels in a dose-dependant pattern. A well-combined dose-dependent and time-dependent effect of CHCl(3) on MT levels after acute and subacute exposure was noticed. Moreover, the increase of MT levels seems to be associated with the GSH depletion, indicating a possible role of the latter in MT synthesis. In conclusion, the superoxide anion production and the GSH depletion could be implicated in the mechanism of hepatotoxity of CHCl(3) and MTs seem to be a part of the antioxidant defense system against the oxidative damage caused by CHCl(3) in liver.
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PMID:Chloroform-induced oxidative stress in rat liver: Implication of metallothionein. 2052 63


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