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 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.
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PMID:Misoprostol hepatoprotection against ischemia-reperfusion-induced liver injury in the rat. 149 53

Endotoxin administration causes liver injury. Patients with alcoholic liver disease frequently have portal vein and systemic endotoxemia, and some investigators have suggested that endotoxin plays an etiologic role in alcoholic liver injury. Many of the metabolic effects of endotoxin are mediated by the cytokine tumor necrosis factor (TNF). It was the purpose of this study to determine whether TNF plays a role in ethanol-enhanced endotoxin liver injury. Rats were fed either a diet in which 36% of the calories were from ethanol or an isocaloric control diet. After 6 weeks, groups of 10 rats were intravenously injected with either saline, 1 mg/kg endotoxin, or 30 micrograms/kg of a prostaglandin E1 (PGE1) analogue + 1 mg/kg endotoxin 24 hr prior to sacrifice. Ethanol/endotoxin-treated rats had significantly higher liver enzyme levels (ALT: 1064 +/- 355 IU/liter, AST: 2024 +/- 515 IU/liter) compared with isocaloric/endotoxin controls (ALT: 237 +/- 54 IU/liter, AST: 602 +/- 80 IU/liter). Ethanol/endotoxin rats also had significantly higher peak serum TNF concentrations (992 +/- 200 units/ml) compared with isocaloric/endotoxin controls (344 +/- 96 units/ml). Pretreatment of ethanol/endotoxin rats with PGE1 caused significant attenuation of liver injury (ALT: 267 +/- 64 IU/liter, AST: 612 +/- 77 IU/liter) and a diminished serum TNF response. In contrast to chronic ethanol administration, acute gavage with 2 mg/kg ethanol (30% w/v) followed by intravenous injection of 2 mg/kg endotoxin produced significantly lower peak serum TNF concentrations (401 +/- 76 units/ml) than gavage with distilled water (1152 +/- 208 units/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor in alcohol enhanced endotoxin liver injury. 153 Jan 27

The effects of induced hypotension with sevoflurane and PGE1 (Group S) on liver functions during neurosurgery that can avoid direct invasion of the liver were retrospectively studied in 35 cases, in comparison with 8 cases of isoflurane and PGE1 induced hypotension (Group I). GOT, GPT and gamma-GTP increased slightly in both groups 1 day and 1 week after operation, but they returned to preoperative levels 1 month later. ChE decreased in both groups, and the decrease was greater in group S. Three cases in Group S (8.6%) and one case in Group I (12.5%) showed GOT or GPT over 100 and there was no significant difference in the two groups. Hypotensive anaesthesia induced with sevoflurane and PGE1 in neurosurgery, as that induced with isoflurane and PGE1, has little effect on postoperative liver functions.
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PMID:[The effects of induced hypotension with sevoflurane and PGE1 on liver functions during neurosurgery]. 160 53

Twenty one patients who underwent prolonged surgical procedures over 10 hours under total intravenous anesthesia with droperidol, fentanyl and ketamine were studied to evaluate post-operative hepatic and renal functions as judged by serum levels of GOT, GPT, BUN and creatinine. They were divided into two groups. Ten patients of the PGE1 group were given PGE1 at a rate of 0.035 micrograms.kg-1.min-1 during anesthesia, and the remaining eleven of the control group were not given PGE1. The two groups were comparable concerning, age, body weight, height, operation time and anesthesia time. In the PGE1 group, significantly more intraoperative fluid was given than in the control group. The blood loss was more but insignificantly in the PGE1 group than in the control group. There was no significant difference in urine output and the amount of blood transfused between the two groups. In both groups, post-operative s-GOT and s-GPT levels were increased significantly compared with pre-operative values, but there was no significant difference between the two groups. Serum BUN levels of the 7-10 the post-operative days were increased significantly in the PGE1 group, but those of the control group were not. These data suggest that our method of total intravenous anesthesia with droperidol, fentanyl and ketamine, when applied even for prolonged surgical procedure over 10 hours, would have beneficial effects on the post-operative hepatic and renal functions.
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PMID:[Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--10. Effects of prostaglandin E1 on the hepatic and renal functions following prolonged surgery under total intravenous anesthesia]. 176 23

An animal model of hepatocytic necrosis was established with injection of D-galactosamine into peritoneal cavity. Examination at regular intervals after injection showed that the level of increased serum TB, ALT and GST and the degree of histological changes in the liver were less marked in PGE-treated animals (n = 34) than those in PGE-untreated animals (n = 29), suggesting that PGE has definite protective effect for experimental hepatocytic necrosis. According to severity of the condition hepatic failure was divided into early stage, typical stage and late stage. A treatment group of 55 cases received PGE1 therapy and a control group basic support therapy only. The results showed that difference of the total effective rate was not significant between the two groups, but in the early stage of hepatic failure, the effective rate in the treatment group was markedly higher than that in the control group. In addition, incidence of hepato-renal syndrome was lower in the treatment group. We are of the opinion that division of severe viral hepatitis into three stages for evaluation of therapeutic effect is rational and useful and early use of PGE1 may show certain efficacy.
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PMID:[Protective effect of prostaglandin E on hepatocytes and its value of early treatment of severe viral hepatitis]. 203 89

Prostaglandin E1 was administered to 19 patients to induce hypotension during intracranial surgery. Urine volume during the operation and after the first day was well maintained, and serum BUN and creatinine were within normal ranges after the surgery. Serum GOT and GPT increased significantly on the 7th and 14th day after the operation compared with the control, but this did not seem to be the results of PGE1 administration. LDH and ALP showed no significant change. Thirty minutes and two hours after the administration of PGE1, arterial blood oxygen tension decreased significantly. These results suggest that PGE1 does not adversely affect the liver and kidneys, and it can be used safely and is useful to control blood pressure during intracranial operation.
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PMID:[Clinical use of prostaglandin E1 during intracranial surgery]. 238 55

The protective effects of PGE1 on ischemia-related liver damage were evaluated in dogs. Ninety minutes warm hepatic ischemia was induced by the total clamping of hepatic inflow vasculatures with portal bypassing. The survival rate improved up to 62.5% when PGE1 was administered intravenously prior to ischemia, while no dog survived for longer than 1 week in the nontreated group. Hepatic ATP content was restored up to 80% of preischemic level 2 h after reflow in the PGE1 pretreated group, compared to 55% recovery in the nontreated group. Complete normalization of hepatic energy charge and rapid decrease of lactate were also seen in the PGE1 group. The clearance rate of intravascular lipid emulsion remained fairly normal in the PGE1 group, thereby suggesting well-preserved hepatic reticuloendothelial functions. The serum activities of beta-glucuronidase, GOT and GPT were suppressed in the PGE1-pretreated group, thereby implying a well-protected hepatic integrity. The histology revealed well-preserved hepatic architecture. The remarkable cytoprotective effect of PGE1 on hepatic ischemia shown in this study indicates that PGE1 warrants further study for protection of ischemically compromised hepatic allografts.
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PMID:Protective effect of prostaglandin E1 (PGE1) on energy metabolism and reticuloendothelial function in the ischemically damaged canine liver. 292 40

Prostaglandins appeared protective against acute experimental liver injury of different origin. Misoprostol, stable, orally active, synthetic derivative of PGE1 attenuates several functional alterations in liver mitochondria during ethanol administration. To study its possible hepatoprotective effects on ethanol-induced liver injury in rats we measured: serum activities of alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (GGT) and concentrations of ammonia in blood and liver tissue. Histopathological evaluation of liver slices was also performed. Activities of both enzymes and ammonia values were elevated after intragastric ethanol administration for 60 days. Treatment for 30 days with misoprostol resulted in their decrease. This effect was not observed in the control group. Beneficial results were also obtained in histopathological evaluation of the liver tissue. These results indicate potential therapeutic effects of misoprostol on ethanol-induced liver injury in rats.
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PMID:Effect of misoprostol in ethanol-induced liver injury. 749 39

The liver has been judged relatively resistant to ischemia, but prolonged inflow occlusion at normothermic conditions can produce evidence of reversible or irreversible hepatocellular damage. Cytoprotective agents have been used both experimentally and clinically to afford extended viability of hepatocytes under reduced perfusion. One agent, prostaglandin E1, has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify this observation in an experimental model using prolonged normothermic inflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepatic artery, choledochal vessels) to allow for sufficient splanchnic decompression. Half of the animals received pretreatment with prostaglandin E1 (alprostadil) 500 micrograms intravenously. Inflow occlusion was maintained for 2 hours followed by reperfusion and killing 24 hours later. As a measure of functional preservation, the tissue adenine nucleotides adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-performance liquid chromatography during occlusion and after reperfusion. Cytosolic enzyme determinations (aspartate transaminase, alanine transaminase, lactate dehydrogenase) were also made before occlusion and after reperfusion. As a possible indicator of cellular injury, blood ionized Ca++ was measured before inflow occlusion and after reperfusion. Although no difference was found in levels of AMP and ADP between prostaglandin E1 and control animals, ATP levels rose significantly higher during recovery in prostaglandin E1 animals at 60 minutes and 24 hours after reperfusion (13.97 +/- 1.29 and 13.60 +/- 0.91 mumoles/gm dry weight prostaglandin E1 vs. 9.25 +/- 0.97 and 9.80 +/- 0.85 mumoles/gm dry weight co control, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of prostaglandin E1 on liver adenine nucleotides and cytoplasmic enzymes in a porcine model of normothermic hepatic ischemia. 759 Jun 75

Effect of LipoPGE1 on liver injury caused by ischemia-reperfusion were compared with that of PGE1-CD, cyclodextrin clathrated PGE1, in rats. LipoPGE1 (10 micrograms/kg) and PGE1-CD (10 micrograms/kg) were gradually injected into the portal vein 5 min both prior to ischemia and prior to reperfusion. In only the group receiving injections of vehicle alone, rats died within 2 days after the episode of 90-min liver ischemia. The survival rate of all rats treated with LipoPGE1 was higher than that of rats who received vehicle alone, which indicates that LipoPGE1 pretherapy improved the survival of rats after liver ischemia-reperfusion. LipoPGE1 markedly suppressed elevations of GOT, GPT, and LDH, lipid peroxide and aromatic amino acid levels in the plasma caused by ischemia-reperfusion of the liver. When animals were given a single dose of LipoPGE1 prior to reperfusion, LipoPGE1 also suppressed elevations of GOT, GPT, LDH and lipid peroxide levels caused by 30-min of liver ischemia followed by 12-hr reperfusion. These suppressive effects with LipoPGE1 were stronger than those of PGE1-CD. These findings suggest that LipoPGE1 may have therapeutic applications in the treatment of hepatic injury.
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PMID:[Protective effects of LipoPGE1, prostaglandin E1 incorporated in lipid microspheres, against liver injury caused by ischemia-reperfusion]. 773 95


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