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)

The hepatoprotective effects of misoprostol, a PGE1 analog, against ischemia-reperfusion liver injury were studied using a rat partial liver ischemia model. Serum ornithine carbamoyltransferase (OCT) and alanine aminotransferase (ALT) levels were determined as biochemical indices of injury. Hepatic cell necrosis was assessed histologically using tetranitroblue tetrazolium (TNBT) and hematoxylin and eosin (H&E) staining. With placebo treatment, 90 min of partial hepatic ischemia followed by 24 hr of reperfusion resulted in increased levels of serum OCT (760 +/- 521 IU/liter) and ALT (4327 +/- 1982 IU/liter), while extensive hepatic necrosis was evident by TNBT and H&E staining. Treatment with two doses of 25 micrograms misoprostol/kg body weight at 1 min before ischemia and 1 min before reperfusion significantly reduced the serum levels of OCT and ALT (207 +/- 189 IU/liter, P less than 0.01 and 2075 +/- 1217 IU/liter, P less than 0.01, respectively) and hepatic necrosis. When a single dose of misoprostol was administered 1 min before reperfusion, similar protective effects were observed. However, when the treatment of misoprostol was delayed to 1 min after reperfusion, significantly less hepatoprotection was seen. Misoprostol exerted no hepatoprotection at all when it was administered at 5 min or later after reperfusion. These results demonstrate that misoprostol partially protects the liver against ischemia-reperfusion injury in the rat. The observation that the protective effect of misoprostol occurs only within the first minute of reperfusion suggests that its mechanism of action involves an early event in reperfusion injury, such as modifying the effects of reactive oxygen metabolites.
 ...
PMID:Misoprostol hepatoprotection against ischemia-reperfusion-induced liver injury in the rat. 149 53

It is not known whether the histopathology of the liver allograft can be predicted from biochemical measurements in serum with the same confidence as in the native liver. To answer this question we compared the histopathological diagnoses in 170 biopsy specimens from 70 adult transplant recipients obtained during the first 180 days, with the concentrations of the serum bilirubin and the activities of AST, ALT and alkaline phosphatase measured at the same time. The most frequent diagnosis was cholestasis (n = 45), which was mild, moderate or severe and which may have been complicated by rejection (n = 28) or ischemia (n = 14). Hepatitis (n = 14), ischemia with rejection (n = 6) and spotty focal necrosis (n = 6) were diagnosed less frequently. Fifteen biopsy specimens were reported as histopathologically normal. In general, biochemical measurements discriminated poorly between different histopathological diagnoses. The histopathologically normal liver often showed an abnormal pattern of enzymes and an increase in the serum bilirubin level. As a result histopathologically normal biopsy specimens were indistinguishable biochemically from those with hepatitis. When two pathological conditions were found to coexist (e.g., cholestasis with either rejection or ischemic necrosis, or ischemic necrosis with rejection), the effect on the serum biochemistry was usually not additive and in some instances returned the biochemical abnormalities toward normal. With the exception of the serum bilirubin level, which increased with the severity of uncomplicated cholestasis, we could not identify a specific pattern of biochemical changes corresponding to a given histopathological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Biochemical and histopathological correlation in liver transplant: the first 180 days. 150 12

The present study evaluated the effect of glycyrrhizin (GR) on an injury of the liver caused by ischemia-reperfusion in rats. In the liver ischemia-reperfusion model, levels of serum GOT, GPT and LDH activities and lipid peroxides in the liver tissue were significantly increased. On the contrary, total glutathione content in the liver tissue and NADPH cytochrome P-450 reductase activity of liver microsomes were decreased. Pretreatment with GR 20 mg/kg, i.v. 10 min before induction of ischemia resulted in significant decreases in serum GOT, GPT, LDH activities and the lipid peroxide level and a higher tissue glutathione content during the period of reperfusion. Electron microscopic studies revealed various hepatocellular damages with an almost intact sinusoidal endothelium in ischemia-reperfused livers. However, the degree of damage was less severe in the livers from the rats pretreated with 20 mg/kg GR. The results indicate that GR is able to provide partial protection against ischemia-reperfused damage.
 ...
PMID:Attenuation of dysfunction in the ischemia-reperfused liver by glycyrrhizin. 151 71

The purpose of this study was to determine whether hepatic tissue oxygenation after ischemia-reperfusion procedures is an indicator for later liver injury. Partial ischemia in the liver was induced by ligating the left pedicles. Rats were divided into two groups according to duration of ischemia: group A (30-min ischemia) and group B (60-min ischemia). Indices of blood oxygenation and blood volume in regional hepatic tissue, serum ALT levels and histological appearance of livers were evaluated. Twenty-four hours after ischemia and reflow, all rats in group A were alive, whereas only 67% survived in group B. Blood-oxygenation index and blood-volume index in group A rats rebounded quickly after reperfusion. In group B, blood-oxygenation index and blood-volume index remained significantly lower than in group A after reperfusion. Serum ALT levels at 60 and 120 min after reperfusion in group B were significantly higher than those in group A. Blood-oxygenation index measured at 5 and 60 min of reperfusion showed significant correlation with serum ALT levels at 120 min of reperfusion. When the percentage recovery of blood-oxygenation index at 5 and 60 min after reperfusion was more than 75%, all rats survived. No obvious signs of hepatocellular degeneration were observed histologically 5 min after reperfusion; however, substantial hepatocellular degeneration had occurred at 120 min of reperfusion in groups A and B. These data indicate that a decline in hepatic tissue oxygenation during the early phase of reperfusion (even when no obvious hepatocellular degeneration has been observed) can be a predictor of subsequent liver injury and prognosis.
 ...
PMID:Hepatic tissue oxygenation as a predictive indicator of ischemia-reperfusion liver injury. 154 23

To evaluate the effects of hepatic inflow occlusion without the shunt, the physiological differences were compared in three groups of rats in which the hepatoduodenal ligament was occluded for 15 min, 30 min, and 60 min. The survival rate significantly decreased in the 60 min occlusion group (53.6%) when compared with that of the 15 min and 30 min occlusion groups (95% and 91.6%, respectively). The significant differences in the changes in blood pressure (BP), the values of plasma potassium, histamine (HIS), norepinephrine (NE), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the values of hematocrit (HT) were also observed between the 30 min and 60 min occlusion groups. The results indicate that, in rats, there is a high probability of an irreversible state to shock after 30 min hepatic inflow occlusion when veno-venous bypass is not applied. The values of plasma HIS and NE and the values of HT in portal blood were significantly greater than those in the general circulation. The results suggest that splanchnic congestion may have a greater influence than hepatic ischemia has in contributing to the deterioration of the physiological state.
 ...
PMID:Effects of hepatic inflow occlusion on changes in plasma potassium, histamine, and norepinephrine in rats. 162 73

Using liver allografts with warm or cold ischemia, we evaluated functional and morphological alterations in hepatocytes, sinusoidal endothelial cells and Kupffer cells in a rat transplantation model. All recipients of allografts with either 4 hr of cold or 30 min of warm ischemia lived more than 22 days and were judged viable. On the other hand, all recipients of grafts with 6 hr of cold or 60 min of warm ischemia died within 2 days and were therefore judged to be nonviable. With these viable and nonviable allograft models, hepatocyte function was evaluated by the bile output and serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and serum lactate dehydrogenase levels; endothelial cell function was judged by the serum hyaluronic acid level, and Kupffer cell function was measured by an intravenous colloidal carbon clearance test. Hepatocyte injury was the prominent feature in warm ischemic grafts, especially in the nonviable ones. On the other hand, serum hyaluronic acid values were significantly higher in the nonviable cold ischemic group, compared with the viable counterpart, suggesting that the functional depression of endothelial cells was predominant in cold, nonviable livers. Histological examinations coincided with the above findings. The phagocytic activity of Kupffer cells was depressed by warm or cold ischemia, whereas the number of Kupffer cells was reduced in the warm ischemia group. We conclude that in liver allografts the main site of injury in warm ischemia is the hepatocytes and suggest that cold ischemia is associated with endothelial cell damage.
 ...
PMID:Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats. 163 55

Effects of glycyrrhizin (GR) on an injury of the liver caused by ischemia-reperfusion in rats were determined. In the liver ischemia-reperfusion model, levels of serum AST, ALT and LDH, lipid peroxides in the liver tissue, and blood superoxide dismutase activity were significantly increased. On the contrary, total glutathione content in the liver tissue was decreased. When rats were given GR 100 mg/kg for 10 days, GR suppressed the elevation of the lipid peroxide level, serum AST, ALT, LDH level, and the decrease in glutathione content during the period of reperfusion. The suppressive effect of GR was similar with that of alpha-tocopherol (VE). GR showed neither 1,1-diphenyl-2-picrylhydrazyl (DPPH) nor 5,5-dimethyl-1-pyrroline-N-oxide(DMPO)-OOH radical-trapping ability, but exhibited DMPO-OH radical-trapping action, while, VE exhibited both DPPH and DMPO-OOH radical-trapping ability. These results indicate that the hydroxyl radical trapping action of GR is the likely mechanism suppressing liver injury caused by ischemia-reperfusion.
 ...
PMID:The protective effect of glycyrrhizin against injury of the liver caused by ischemia-reperfusion. 165 Jan 69

The effect of FK 506 on regeneration of the liver was studied in rats after a two-thirds partial hepatectomy after 60 min of ischemia of the unresected liver. The animals were divided into three distinct groups of 10 rats each. Group 1 (controls) received 0.5 ml saline solution intravenously 30 min after the induction of ischemia. Groups 2 and 3 were injected with FK 506 (0.3 mg/kg) intravenously 30 min after and 24 min before the induction of hepatic ischemia, respectively. The hepatic content of ATP and serum levels of ALT and lactate dehydrogenase were determined on each animal. In addition, the histological appearance and mitotic activity of the remnant liver was determined at regular 24-hr intervals after hepatic ischemia. All 10 control animals died within 72 hr. Treatment with FK 506 resulted in improved survival in groups 2 and 3 (30% and 80%, respectively). The improved survival seen in the FK 506-treated animals was reflected by a restoration of hepatic ATP content, a reduction in the serum levels of ALT and lactate dehydrogenase, an amelioration of hepatic necrosis and neutrophilic infiltration and an increase in the mitotic activity of the liver. These results suggest that FK 506 ameliorates the hepatic injury associated with ischemia/reperfusion and has a potent stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective agent when administered to organ donors before graft harvesting.
 ...
PMID:FK 506 ameliorates the hepatic injury associated with ischemia and reperfusion in rats. 170 12

The effect of ischemia on hepatic protein synthesis during sepsis is not known, but is of clinical relevance, since hepatic blood flow decreases during the late phase of sepsis. In this study, synthesis of acute-phase proteins was measured in perfused livers of rats 16 hours after sham operation or cecal ligation and puncture. Livers from each group had 45 minutes of complete ischemia or control perfusion. Protein synthesis was measured during two hour perfusion after the ischemia or control period, by determining incorporation of 3H-leucine into total secreted trichloracetic acid precipitated proteins, immunoprecipitated complement component C3 and albumin and phosphotungstenate-precipitated alpha 1-acid glycoprotein. Lactate, glutamine-oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in the perfusate were measured during preischemic and postischemic perfusion. Tissue glutathione levels were measured at the end of the perfusion. Synthesis of alpha 1-acid glycoprotein was increased by 100 per cent and albumin synthesis decreased by 46 per cent in septic livers, consistent with an acute-phase response and apparent downregulation of albumin synthesis during early sepsis. Synthesis rates were reduced by 50 to 60 per cent after ischemia in perfused livers from sham operated rats and 70 to 80 per cent in livers from septic rats. Hepatic production of interleukin-1 was not different between the groups during perfusion. GOT and GPT levels increased significantly during ischemia of both nonseptic and septic livers and rapidly returned toward baseline during reperfusion. Lactate levels were higher in perfusate of septic than of nonseptic livers before ischemia and increased further during ischemia. The results suggest that ischemia inhibits production of secreted hepatic proteins similarly in nonseptic and septic livers, but perhaps to a slightly greater extent in septic livers.
 ...
PMID:Effect of ischemia on protein synthesis in the septic liver. 170 61

This study was done to determine the relationship between microsomal lipid peroxidation during hepatic ischemia/reperfusion and alteration in cytochrome P-450-dependent drug metabolism. Rats were pretreated with alpha-tocopherol to inhibit lipid peroxidation or with vehicle (soybean oil) and then subjected to 60 min no-flow hepatic ischemia in vivo. Control animals were time-matched sham-ischemic animals. After 1, 5 or 24 hr of reperfusion, liver microsomes were isolated and cytochrome P-450 and mixed function oxidases were studied. In vehicle-treated ischemic rats, serum ALT levels peaked at 5 hr (5,242 +/- 682 U/L) and were significantly reduced by alpha-tocopherol pretreatment (1,854 +/- 229 U/L, p less than 0.01). Similarly, microsomal lipid peroxidation was elevated in the vehicle-treated ischemic group, but this elevation was prevented by alpha-tocopherol pretreatment. Microsomal cytochrome P-450 content and aminopyrine-N-demethylase activity were both decreased in vehicle-treated ischemic rats to 60% and 70% of sham-ischemic control levels, respectively. Although alpha-tocopherol restored cytochrome P-450 content to the level of sham-ischemic control rats, aminopyrine-N-demethylase activity remained at 76% of control with alpha-tocopherol treatment (p less than 0.01 compared with sham-ischemic control). In contrast to what was seen with cytochrome P-450 and aminopyrine-N-demethylase, aniline p-hydroxylase activity was elevated in the vehicle-treated ischemic rats compared with sham-ischemic control rats. These increases were prevented by alpha-tocopherol pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of alpha-tocopherol on hepatic mixed function oxidases in hepatic ischemia/reperfusion. 173 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>