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)

The expression of albumin and alpha 1-inhibitor 3 genes was investigated in rat cell suspensions enriched in periportal (n = 10) and perivenous (n = 10) hepatocytes obtained by the digitonin-collagenase technique. The degree of enrichment of the cell suspensions was assessed: (1) by enzymic assays for the periportal marker alanine aminotransferase and for the perivenous marker glutamine synthetase; and (2) by their content of mRNAs for the periportal marker hepatic glutaminase and for glutamine synthetase. The existence of an antegrade intra-lobular gradient for albumin and alpha 1-inhibitor 3 mRNAs was demonstrated, with periportal:perivenous ratios of 2.33 and 3.80, respectively. However, no gradient was demonstrated for the respective protein contents with corresponding ratios of 0.98 and 1.21. A certain degree of overlap existed between periportal and perivenous suspensions for their content in albumin and alpha 1-inhibitor 3 mRNAs. A morphometrical analysis of the surface of digitonin-permeabilized hepatic tissue revealed that this overlap could be explained by a variable extent of permeabilization of the mediolobular zone from one rat to another and from one lobule to another in a given animal. These results suggest that while the digitonin-collagenase technique is well suited for studies in vitro of proteins expressed in sharp intra-lobular gradients or restricted to an intra-lobular compartment, it is not completely reliable for proteins distributed in continuous moderate intra-lobular gradients, such as albumin and alpha 1-inhibitor 3.
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PMID:Distribution of albumin, alpha 1-inhibitor 3 and their respective mRNAs in periportal and perivenous rat hepatocytes isolated by the digitonin-collagenase technique. 782 39

Chloroform (CHCl3) is widely used in the manufacture of drugs, cosmetics, plastics and cleaning agents. It is also found in chlorinated drinking water. This study was designed to investigate the toxic effect of CHCl3 on isolated male rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and the cell viability was determined by Trypan blue exclusion. The leakage of cytosolic enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) after treatment with CHCl3 was measured. Reduced glutathione content (GSH) and its related enzymes, glutathione reductase (GSH-Rx) and glutathione peroxidase (GSH-Px), were also evaluated to study the effect of CHCl3 on hepatocytes. Exposure to 100 and 1000 ppm CHCl3 results in a significant decrease in cell after 30 min incubation. However, the effect of 1 and 10 ppm concentrations was observed at 60 min incubation. AST leakage was significantly increased in all treatment groups, while ALT was significantly increased at 100 and 1000 ppm CHCl3 after 60 and 30 min, respectively. As early as 15 min, GSH was decreased significantly at 1000 ppm, but at 100 and 10 ppm CHCl3 the decrease in GSH began after 30 and 120 min, respectively. GSH-Px activity did not changed. However, the activity of GSH-Rx was significantly decreased at 1000 ppm CHCl3 and at the same time GSH content was decreased. The data indicate that the toxic effect of CHCl3 was dose- and time-dependent. The degree of GSH depletion correlated with increased cytotoxicity and decreased GSH-Rx activity due to CHCl3.
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PMID:The mechanism of chloroform toxicity in isolated rat hepatocytes. 835 69

Mercury is the major component of dental amalgam restorative material, which typically has 50% pure elemental mercury. It is also used in some skin creams, and in the manufacturing of plastic, drugs and fungicides. The present study was designed to investigate the toxicity of methyl mercury (MeHg+) on isolated rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and were incubated with different concentrations of MeHg+ (0.1-100 ppm) for 2 h. Through the incubation period the viability was determined by Trypan blue exclusion. Reduced glutathione (GSH) content and its enzymes, glutathione peroxidase (GSH-PX) and glutathione reductase (GSH-RX) were measured. Leakage of enzymes such as aspartate transaminase (AST), and alanine transaminase (ALT) were determined. The cell viability was reduced significantly after 1 h incubation when 0.1 and 1 ppm MeHg+ were applied. The decrease in the cell viability was dose- and time-dependent. A depletion of GSH content was observed with 100 ppm MeHg+ after 30 min of incubation. A significant decrease in GSH-RX was observed with 100 ppm during 15 and 30 min of incubation, while 10 ppm of MeHg+ significantly increased ALT leakage after 60 min. However, there was a significant increase in AST leakage with 100 ppm only. The present investigation indicates that the toxic effect of MeHg+ is most likely cytosolic enzyme related.
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PMID:The mechanism of methyl mercury toxicity in isolated rat hepatocytes. 835 70

Cypermethrin is a synthetic pyrethroid that belongs to a group of insecticides with low mammalian toxicity but high insecticidal activity. The present study was designed to investigate the toxicity of cypermethrin on freshly isolated hepatocytes from male and female rats. Hepatocytes were harvested by a collagenase perfusion technique and were exposed to different concentrations of cypermethrin (100, 200, 400, or 800 ng/2 x 10(6) cells) for up to 2 h. Cell viability and the leakage of aspartate transaminase (AST) and alanine transaminase (ALT) were determined throughout the incubation period. The cell viability of the hepatocytes from male and female rats exposed to 400 ng and 800 ng was significantly reduced after 60 and 30 min of incubation, respectively. With cells from female rats, viability was also reduced upon exposure to 200 ng cypermethrin for 2 h. The decrease in cell viability was dose and time dependent. The leakage of ALT and AST was significantly increased with 400 and 800 ng concentrations at 60 and 30 min, respectively. ALT leakage from female hepatocytes was significantly increased at 60 min of incubation with the 200-ng dose, whereas 2 h of incubation was required for the leakage of ALT from the cells of male rats. The present data indicate that cypermethrin has toxic effects on male and female rat hepatocytes in a dose- and time-dependent manner. The data suggest that female rat hepatocytes may be more sensitive to the toxic effects of cypermethrin than male cells.
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PMID:Effect of cypermethrin on isolated male and female rat hepatocytes. 938 36

During water treatment, potentially hazardous chemical by-products may be formed. Alachlor (2-chloro-N-(2, 6-diethylphenyl)-N-(methoxymethyl) acetamide) is a widely used pre-emergence herbicide. The present study investigated the toxicity of alachlor and its disinfection by-products on freshly isolated rat hepatocytes. Hepatocytes were harvested by a collagenase perfusion technique and were exposed to different concentrations of alachlor and its by-products for up to 2 h. Cell viability, the leakage of aspartate transaminase (AST) and alanine transaminase (ALT) and glutathione (GSH) depletion were determined throughout the incubation period. The cell viability of the hepatocytes exposed to 100 microg ml(-1) alachlor was decreased by 20% compared with the control after 60 min of incubation. At the same concentration of alachlor the leakage of ALT and AST was increased by 56% and 45%, respectively. Cell viability of the hepatocytes was decreased upon exposure to 2-chloro-N-(3-chloro-2,6-diethylphenyl)-N-(methoxymethyl) acetamide (CCDMA) and 2-chloro-N-(3-chloro-2,6-diethylphenyl) acetamide (CCDA)--the by-products of alachlor and chlorine--after 60 min of exposure. At 100 microg ml(-1) CCDMA the AST leakage was increased significantly (73%) after 30 min of incubation. The reaction mixture of alachlor (100 microg ml(-1)) and chlorine dioxide (1 ppm) caused significant increases in cell loss and ALT and AST levels by 22%, 40% and 34%, respectively, as early as 15 min incubation. Alachlor (100 and 200 microg ml(-1)) caused significant decreases in GSH contents (62%) in isolated hepatocytes. The reaction mixture of alachlor and chlorine dioxide led to significant glutathione depletion (44%) after 60 min of incubation. The by-products of alachlor and chlorine--CCDMA and CCDA--depleted GSH almost completely (93%). This investigation suggested that the by-products formed from the reaction of alachlor and chlorine decreased GSH and increased the leakage of liver enzymes, especially AST.
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PMID:In vitro hepatotoxicity of alachlor and its by-products. 1180 27

The aim of this study was to configure a new bioartificial liver (BAL) support system and evaluate its functions in vitro. Chinese experimental miniature pig hepatocytes were isolated by an in situ recirculating collagenase perfusion method and were cultured in serum-free medium with restriction attachment and spinner technique to form hepatocyte spheroid suspensions containing 1.0 x 10(10) hepatocytes. The BAL support system was configured by inoculating the hepatocyte spheroids into the cell circuit of a hollow fiber bioreactor (BIOLIV A3A, Cell Biotech Limited, HK, China). The number and viability of hepatocytes, the levels of alanine aminotransferase (ALT), total bilirubin (TBi), and albumin (ALB) in the circulating hepatocyte suspension and RPMI-1640 medium, and lidocaine metabolism were determined during 6 hr of circulation in the BAL devices. Independent experiments were performed 5 times. There were no significant changes in the number and viability of the hepatocytes during the circulation period. The BAL support system demonstrated substantial albumin synthesis and lidocaine metabolism. The results indicate that the new BAL support system has the ability to perform liver functions and could be used to treat liver failure or provide temporary liver support in patients who are candidates for liver transplantation.
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PMID:Configuration of a new bioartificial liver support system and in vitro evaluation of its functions. 1583 Jul 4

The aim was to investigate the suppressive effect of bicyclol on hepatic fibrosis induced by dimethylnitrosamine (DMN) in mice and the mechanism of its action. Hepatic fibrosis was established by intraperitoneal injection of 8 mg kg(-1) day(-1) on three consecutive days of each week for 4 or 5 weeks. In the prophylactic experiment, bicyclol (100 and 200mg.kg(-1)) was administered by gavage in association with DMN injection. For the therapeutic experiment, mice were firstly injected with DMN for 5 weeks as in the prophylactic experiment, and then the mice in drug groups were orally administered bicyclol (100 and 200mg.kg(-1)) once daily for 5 weeks. As a result, the levels of alanine aminotransferase (ALT), total bilirubin, hydroxyproline (Hyp), prolidase, tumor necrosis factor-alpha (TNFalpha), transforming growth factor beta-1 (TGFbeta(1)), type I collagen in serum and the score of liver fibrosis all significantly increased in the hepatic fibrosis model group in comparison with those in control group. The treatment with bicyclol markedly reduced all the above criteria. Bicyclol also attenuated the decrease of body weight of mice, serum total protein and albumin. In addition, bicyclol treatment inhibited liver TGFbeta(1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA expression in the prophylactic experiment. Similarly, bicyclol reduced TIMP-1 levels in liver and serum and increased collagenase activity in the liver in the therapeutic experiment. The result suggest that bicyclol attenuates DMN-induced hepatic fibrosis in mice. Its mechanisms of action may be related to the hepatoprotective and anti-inflammation properties, the down-regulation of liver TGFbeta(1) and TIMP-1 expression and the increase of net collagenase activity in liver.
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PMID:Effects of bicyclol on dimethylnitrosamine-induced liver fibrosis in mice and its mechanism of action. 1660

Despite pathophysiological similarities to alcoholic liver disease, susceptibility to acetaminophen hepatotoxicity in metabolic syndrome-related nonalcoholic steatohepatitis (NASH) has not been well elucidated. In this study, therefore, we investigated acetaminophen-induced liver injury in KK-A(y) mice, an animal model of metabolic syndrome. Twelve-week-old male KK-A(y) and C57Bl/6 mice were injected intraperitoneally with 300 or 600 mg/kg acetaminophen, and euthanized 6 h later. Liver histology was assessed, and hepatic expression of 4-hydroxy-2-nonenal was detected by immunohistochemistry. Levels of reduced glutathione were determined spectrophotometrically. Phosphorylation of c-Jun NH(2)-terminal kinase (JNK) was analyzed by Western blotting. Hepatocytes were isolated from both strains by collagenase perfusion, and cell death and oxidative stress were measured fluorometrically by use of propidium iodide and 5-(and-6)-chloromethyl-2'7'-dichloro-dihydrofluorescein diacetate acetyl ester, respectively. Acetaminophen induced more severe necrosis and apoptosis of hepatocytes in KK-A(y) mice than in C57Bl/6 mice and significantly increased serum alanine aminotransferase levels in KK-A(y) mice. Acetaminophen-induction of 4-hydroxy-2-nonenal in the liver was potentiated, whereas the levels of reduced glutathione in liver were lower in KK-A(y) mice. Acetaminophen-induced phosphorylation of JNK in the liver was also enhanced in KK-A(y) mice. Exposure to 20 microM tert-butyl hydroperoxide did not kill hepatocytes isolated from C57Bl/6 mice but induced cell death and higher oxidative stress in hepatocytes from KK-A(y) mice. These results demonstrated that acetaminophen toxicity is increased in diabetic KK-A(y) mice mainly due to enhanced oxidative stress in hepatocytes, suggesting that metabolic syndrome-related steatohepatitis is an exacerbating factor for acetaminophen-induced liver injury.
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PMID:Diabetic KK-A(y) mice are highly susceptible to oxidative hepatocellular damage induced by acetaminophen. 2053 6

Acrylamide (ACR) is an important industrial chemical used primarily in the production of polymers and co-polymers. Acrylamide is mainly neurotoxic to experimental animals as well as humans and has also been shown to be mutagenic and carcinogenic. The present study was designed to investigate the toxicity of ACR on isolated rat hepatocytes. The hepatocytes were isolated by collagenase perfusion method and were incubated with different concentrations of ACR (0.1, 1, 10mm) for 2 hours. Cell viability by trypan blue exclusion and leakage of the enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST) were determined. Reduced glutathione (GSH), glutathione S-transferase (GST) activity were also measured. A significant decrease in the cell viability was observed after exposure to 10mm ACR for 30min, while 1mm ACR caused a significant decrease in the viability after 60min. ALT leakage was parallel to the cell viability. AST leakage was significantly increased at 30min of incubation with 10mm ACR, whereas 2 hours of incubation was required for the leakage of AST from rats hepatocytes with 1mm ACR. 10mm ACR decreased significantly GSH as early as 30min, while GSH level was decreased at 60min after exposure to 1mm ACR. Also, the GST activity increased with increasing the dose of ACR. Cytochrome P450 concentration was decreased after exposure to 10mm ACR. The effect of ACR on cell viability, ALT and AST leakage, GSH and GST activity was time and dose dependent.
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PMID:Acrylamide toxicity in isolated rat hepatocytes. 2065 59

Amphetamines (AMP) are potent psychostimulants and commonly used drugs of abuse. Its chronic administration creates tolerance and addiction and also associated with neurotoxicity and hepatocellular damage through oxidative stress. The present study was designed to evaluate the cytotoxic effects as well as the oxidative stress induced by d-amphetamines in isolated rat hepatocytes. Hepatocytes were isolated by collagenase perfusion technique and were exposed to different concentrations of AMP (0.2, 0.4, 0.8 and 1.6mM) in a time-course experiment for up to 2h. AMP exposure induced a significant decrease in cell viability and a significant increase in the leakage of hepatic enzymes {lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and asparate aminotransferase (AST)} in a concentration and time-related manner. In the same experiment, GSH content and thiobarbituric acid reactive substances (TBARS) generation were determined as indices of oxidative stress and lipid peroxidation respectively. AMP exposure results in a significant decrease in cellular GSH content as well as a significant enhancement of TBARS accumulation in a concentration and time-related manners. The obtained results suggested that 2-h exposure of hepatocytes to AMP (0.8mM) was accompanied by submaximal responses. Therefore, a subsequent dose-response experiment was designed to evaluate the role of GSH modulation and oxidative stress in AMP toxicity in hepatocytes at 2h. LDH release and TBARS generation were used as indicators in this experiment. Pretreatment with the GSH-depleting agents, chlorodinitrobenzene (CDNB), buthionine sulfoximine (BSO), or bis(chloroethyl)-nitrosurea (BCNU) enhanced the cytotoxicity of AMP. Conversely, pretreatment with GSH or sulfhydryl compounds such as methionine (MT), cysteine (CYS) or dithiothreitol (DTT) attenuated AMP toxicity. Similarly, co-incubation with enzymatic antioxidants, superoxide dismutase (SOD) or catalase (CAT) or iron chelator, desferroxiamine (DFO) or the hydroxyl radical scavengers, dimethylsulfoxide (DMSO) exhibited significant protection against AMP cytotoxicity. The present results indicate that AMP has a potential cytotoxic effect in isolated rat hepatocytes. AMP cytotoxicity is concentration-dependent. GSH depletion and oxidative stress play an important role in enhancing hepatotoxic potential of AMP in isolated rat hepatocyte. Thiol group-donors, antioxidants, free radical scavengers and iron chelators can play a critical role against AMP-induced cellular damage.
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PMID:d-Amphetamine-induced cytotoxicity and oxidative stress in isolated rat hepatocytes. 2157 9


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