Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary cultures of adult rat hepatocytes were incubated (1.5-16 hr) with various concentrations of CCl4 (less than or equal to 0.5 mM) and/or CHCl3 (less than or equal to 2.5 mM). Agent-dependent alterations in hepatocyte functions were assessed by measuring (1) [3H]choline incorporation into phosphatidylcholine (endoplasmic reticulum), (2) MTT (tetrazolium salt) reduction (mitochondria), and (3) AST release into medium (plasma membrane). Cultured hepatocytes incubated with 0.5 mM CCl4 displayed a significant (p less than or equal to 0.001) and rapid (1.5 hr) reduction (40%) in endoplasmic reticulum function that preceded significant (p less than or equal to 0.001) alterations in mitochondria (6-16 hr) and plasma membrane (6-16 hr) functions. CCl4-dependent alterations in liver cell functions are a result of CCl4 bioactivation since metyrapone inhibits the CCl4-mediated changes in cell functions. Response surface methods (RSM) were used to determine the influence of combinations of CCl4 and CHCl3 on liver cell MTT reduction and [3H]choline incorporation. Regression coefficients were determined for CCl4, CHCl3, and CCl4-CHCl3. All results were significant (p less than 0.0001) and implied that CCl4 was a more potent hepatotoxin in vitro than CHCl3. The RSM analysis also suggested that combinations of CHCl3 and CCl4 have greater than additive effects on MTT reduction and [3H]choline incorporation. These effects of CCl4 and/or CHCl3 on liver cell functions in vitro are consistent with liver alterations observed in vivo. Therefore, primary cultures of adult rat hepatocytes may be an appropriate model in vitro to assess the hepatotoxic potential of agents alone or in combination.
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PMID:Toxic interactions between carbon tetrachloride and chloroform in cultured rat hepatocytes. 279 11

The concentration of serum immunoreactive prolyl 4-hydroxylase (S-IRPH) was determined in patients with various liver diseases by the radioimmunoassay developed previously. S-IRPH values were elevated in acute hepatitis (p less than 0.01), hepatocellular carcinoma (p less than 0.05), metastatic liver neoplasm (p less than 0.01) and cholestatic diseases (p less than 0.001), but no significant elevation was seen in chronic hepatitis or liver cirrhosis. The mean value of S-IRPH was highest in cholestatic diseases, and next highest in acute hepatitis. In addition to acute hepatitis, S-IRPH was increased in other conditions of hepatocellular damage such as exacerbation of chronic hepatitis or immediately after transcatheter arterial embolization of hepatocellular carcinoma. In cases of hepatocellular damage S-IRPH varied concurrent with cytoplasmic enzyme (AST, ALT and LDH) levels and in cases of cholestatic diseases with biliary enzyme (Al-P and gamma GTP) levels. These properties appear to be unique among serum enzymes. The characteristics of S-IRPH were considered to be related to its unique subcellular localization within the cell, ie the membrane of rough endoplasmic reticulum.
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PMID:Studies on serum immunoreactive prolyl 4-hydroxylase in liver diseases--its elevation both in hepatocellular damage and cholestatic diseases. 284 41

An increase in relative liver weight, the total liver DNA content, hepatocyte volume and the total surface area of the membranes of mitochondria and the granular and smooth endoplasmic reticulum of hepatocytes, but a decrease in the size of the nuclei, were found in adult male rats fed three weeks on a high protein diet compared with animals given a standard laboratory diet. Serum transaminase (ALT, AST) and alkaline phosphatase activity was practically the same as the control values. Rats fed three weeks on a low protein diet showed a decrease in relative liver weight, in the total liver DNA content, in hepatocyte and nuclear volume and in ploidy, and also in the surface area of the membranes of the mitochondria and the smooth and granular endoplasmic reticulum; conversely, the number of binucleate hepatocytes rose. Serum ALT, AST and alkaline phosphatase activity was mildly, but statistically significantly elevated.
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PMID:Effect of long-term administration of a high protein or low protein diet on rat liver. Morphological and biochemical findings. 294 5

The aim of the study was to evaluate the enzyme activity of cellular membranes (GGT), cytosol (ALT, AST) and lysosome (AP, AcP) in the cytosol, whole homogenate and blood serum during declamping shock, following release of abdominal aorta cross-clamping. The aorta was clamped for 60 minutes. An increase in GGT, AP and AcP activities in the cytosol and whole homogenate of the renal cortex, renal medulla, liver, lung, heart and the skeletal muscle occurs after declamping. Rise in the enzymatic activity, especially of acid phosphatase is higher when the aorta above renal arteries was clamped. However, its activity in the blood serum remains unchanged. Alterations in the distribution and the activity of the studied enzymes may indicate that aortic clamping damages the endoplasmic reticulum and lysosomal membranes. Yet, cellular membranes preserve their structural and functional integrity.
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PMID:Activity of membrane, cytosol and lysosome enzymes in organs and blood serum during declamping shock. 852 88

The role of oxidative stress as a mechanism of hepatic injury caused by isoniazid (INH) was investigated in young growing rats. The interaction of moderate and severe degree of protein-energy malnutrition (PEM) was also investigated. Hepatic injury was produced by giving 50 mg/kg/day of INH for 2 weeks. Liver showed kupffer cell hyperplasia along with patchy sinusoidal congestion in hematoxylin (H) and eosin (E) staining. However, diffuse microglobules of oil red O' positive fat globules could be demonstrated in frozen sections stained with oil red O'. The concomitant elevation of serum ALT/AST added support to the histopathologic injury. Electronmicroscopic analysis revealed the proliferation of rough endoplasmic reticulum in INH-treated groups. The glutathione and related thiols were decreased significantly by INH both in blood and liver tissues, indicating a decrease in protective mechanism. Glutathione reductase activity was elevated concomitantly in both the tissues. A significant decrease in the activity of glutathione peroxidase and catalase is again indicative of diminished capacity to handle the disposal of hydrogen peroxide (H2O2) and lipid peroxides. All these alterations indicated that the damage to the liver cell could well be operating through the inefficient disposal of superoxides (O-2) and H2O2. A profound decrease in the protective mechanism further aggravated the picture in moderate and severe PEM, which was observed with INH alone.
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PMID:Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition. 902 73

The possibility of resuscitating livers after warm ischaemia has been recently suggested. The aim of the present investigation was to analyse the effects of anoxia on the morphology of hepatic cells, to determine whether these effects are reversible after providing a resuscitation period between warm ischaemia (WI) and cooling, and to study the behaviour of the resuscitated liver in the recipient organism. Ten female, Large-White pigs acted as donors for 10 recipient animals of the same kind who received an orthotopic liver graft. Recipients were divided into two groups depending on whether the livers they received had undergone a resuscitation period (Group I (n=5) where animal livers were subjected to 5 min warm ischaemia (WI) without resuscitation, and Group II (n=5) where the livers were subjected to 5 min WI followed by 5 min resuscitation). Morphological and ultrastructural studies of liver cells were performed using light and electron microscopy. ATP, ADP and AMP levels were determined in liver biopsies by high performance liquid chromatography (HPLC). Plasma AST and bilirubin levels in the two groups were compared 24 h after transplantation. After 5 min of anoxia, hepatocytes showed two morphological patterns in response to WI. Some were appreciably condensed with dark mitochondria, peroxisomes and some cytoplasmic vacuoles. Others showed electronlucent organelles, inflamed mitochondria with broken cristae and disorganized endoplasmic reticulum. Hepatocytes showed globular microvilli and bleb formation with migration towards the sinusoids. One hour after the revascularisation of the resuscitated livers, the hepatocytes showed nearly normal morphological characteristics. However, the hepatocytes of non-resuscitated organs continued to show alterations. Kupffer cells were activated in the livers of both experimental groups. Ultrastructural changes and total tissue adenine nucleotide (TAN) levels recovered completely in resuscitated livers soon after transplant. These results suggest that when short WI periods are followed by equivalent periods of resuscitation, the hepatocytes of transplanted livers recover from the effects of anoxia.
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PMID:A histopathological study of anoxic-resuscitated liver allografts. 904 50

In this study, 11,284 mg/m3 (2600 ppm) of xylene was administered for 8 hours a day to pregnant rats by means of inhalation, starting from the sixth day of their pregnancies. Furthermore, while a group of non-pregnant rats inhaled the same amount of xylene during the same period, the control group inhaled clean air. Consequently, in addition to the embryotoxic effects of xylene, the effects on the various tissues of the mothers and their litters were observed light and electron microscopes. No external anomalies were observed in any of the rats born at the end of the 21st day, and there were no macroscopic defects in their organs either. While following xylene inhalation no structural defects in the kidney and pancreas was found, expansions in the smooth endoplasmic reticulum of the liver tissues, increases in the lysosomes, and defective mitochondrion structures were found in the pregnant and non-pregnant rats. It was noticed that xylene in particular caused structural defects in the liver of the fetus. Compared to the control groups, increases were observed in the activities of the AST, ALT, ALP, and Arginase enzymes in the liver.
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PMID:The effect of xylene inhalation on the rat liver. 1010 37

Experiments were carried out on female albino (Wistar) rats to establish ricin's liver damaging effect. In accordance with the data in the literature it seems that: 1. 2 microg/kg i.p. ricin (investigated 24 h later of its administration) has a detectable hepatotoxic effect; i.e. electron density changes of cells and swelling of mitochondria. These findings correspond to the common and first ultrastructural signs of liver cell damage. This result was further strengthened by the fact that serum ALT and AST values were significantly elevated compared to the control value. 2. The next steps of ricin's damaging effect have been detected at 10 microg/kg i.p. dose,--namely: Effect on smooth endoplasmic reticulum: in its place there is a loose, foam-structured unidentified material,--while in the granulated endoplasmic reticulum the number of ribosomes decreased, similarly to the glycogen granules. 3. 200 microg/kg i.p. ricin caused a severe liver-cell damage. The mitochondria showed early degenerative signs,--and both endoplasmic reticulums were further damaged. The most significant feature is the complete lack of ribosomes in the tubular structure of the granulated endoplasmic reticulum. This latter finding enlights the known inhibitory effect of ricin on protein synthesis. The serum enzyme-levels remained in the pathological range. No early sign of enzyme (Cytochrome P450,) induction could be observed.
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PMID:Ultrastructural study of liver cell damage induced by ricin. 1108 92

The objective of the current study was to analyze the hepatotoxic effect caused by cypermethrin (CYP) in rats, and to evaluate the possible protective effect of the antioxidant alpha-tocopherol (alpha-T). Fifty male Wistar rats were given daily i.p. doses of 300 mg/kg per day of CYP during 7 days. Half of them were administered three previous doses of 100 mg/kg per day of alpha-T, followed by seven subsequent oral doses of 40 mg/kg per day of alpha-T. The levels of biochemical indicators and histological liver damage were determined, as well as DCVA in urine. CYP altered the lipid metabolism. Such alterations were inhibited 32% by alpha-T, except for LDL. Alterations in AST were modulated in 29%. In the histology, alpha-T reduced mitochondria damage, and swelling of the endoplasmic reticulum of the liver cells. The results suggest that alpha-T can modify CYP metabolism, changing the lipidic profile and the histological analysis.
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PMID:alpha-Tocopherol modulates liver toxicity of the pyrethroid cypermethrin. 1170 Dec 29

Hepatotoxic effect of (+)usnic acid, the active constituent of Usnea siamensis Wainio was studied in rats, isolated rat hepatocytes and isolated rat liver mitochondria. In rats, after treatment with high dose of (+)usnic acid (200 mg/kg per day, i.p.) for 5 days, there was no significant change in serum transaminase activity (serum AST, ALT) while the electron micrographs showed apparent morphological damage of mitochondria and endoplasmic reticulum. (+)Usnic acid at high dose (1 mM) as well as carbon tetrachloride (CCl4, the reference hepatotoxin) induced loss of cell membrane integrity in isolated rat hepatocytes by increasing the release of cellular transaminases (AST, ALT). Increase in lipid peroxidation, decrease in glutathione (GSH) content and increase in aniline hydroxylase activity (CYP 2E1) were also found. Combination of (+)usnic acid and CCl4 showed the additive results. (+)Usnic acid (0.15-6 microM) possessed uncoupling activity in isolated rat liver mitochondria. It stimulated respiration by mitochondria respiring with glutamate plus malate or succinate as substrates and activated ATPase activity. Increasing concentration of (+)usnic acid (>6 microM) exhibited loss of respiratory control and ATP synthesis. In conclusion, hepatotoxic effect of high dose (+)usnic acid may involve its reactive metabolite(s), causing loss of integrity of membrane like structures, resulting in destruction of mitochondrial respiration and oxidative phosphorylation.
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PMID:Hepatotoxic effect of (+)usnic acid from Usnea siamensis Wainio in rats, isolated rat hepatocytes and isolated rat liver mitochondria. 1501 5


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