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)

Twenty-four young male divers were assigned randomly to 4 treatment groups: Group I received aspirin (325 mg) three times daily; II received dipyridamole (75 mg) three times daily; III received both drug regimens; and IV received matching placebo. Double-blind procedures were followed. Treatment began 24 h prior to a 48-h saturation dive (inclusive of 17 h decompression) at a simulated depth of 18.3 m and continued throughout and for 3 days after the dive. A post-dive reduction in circulating platelet count was observed in all groups, except the group that received aspirin only. Platelet survival was shortened in all treatment groups. Five cases of Type I decompression sickness occurred and were treated by recompression, two in the aspirin plus dipyridamole group, two in the dipyridamole group, and one in the placebo group. Blood chemistry and hematology profiles showed that divers with decompression sickness had more elevated GOT, GPT, CPK, cholesterol and triglyceride levels, and greater reductions in platelet count, Platelet Factor 4 and Thrombin Clotting Time than most other subjects. Subjects receiving either aspirin or aspirin plus dipyridamole had fewer changes in these parameters. Failure of aspirin to potentiate, or add to, dipyridamole may be due to other actions of aspirin such as inhibition of prostacyclin synthesis. Further studies of the role of antiplatelet drugs in decompression sickness are warranted.
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PMID:Effects of aspirin and dipyridamole on platelet function, hematology, and blood chemistry of saturation divers. 53 93

The feasibility of maintaining long-term viability of human venous allografts by cryopreservation has been investigated. Segments of vein were obtained from 85 patients undergoing a stripping operation for varicose veins. The venous segments were immersed in a dimethylsulfoxide 15% solution, deep frozen at -196 degrees C in liquid nitrogen and preserved for a duration of 1 week to 24 months. Light microscopy (n = 126) failed to demonstrate striking differences between control veins and any of the cryopreserved veins. The types of damage observed at scanning electron microscopy included endothelial cell separation, endothelial cell loss, exposed basement membrane and exposed fibrillar collagen, which were graded on a scale. The score for short term (less than 3 weeks) stored veins was 8.1 +/- 0.9 (mean +/- SEM) and did not differ from the long-term (greater than 10 weeks) stored veins score (6.3 +/- 1.0, p NS). The tissue enzymes LDH, GOT, GPT, CPK were measured in the frozen vein groups (n = 115) after thawing to room temperature. Cryopreservation did not alter any of the tissue enzymes measured when compared to controls. Endothelial fibrinolytic activity (FA) of 58 venous segments cryopreserved for a mean duration of 20 months was 6136.4 +/- 292.1 Tissue Activator Units (TAU) and did not differ from FA of 11 controls (5989.1 +/- 696.8 TAU). Synthesis of 6-Keto-PGF1-alpha-2, a stable breakdown product of PGI2, measured in 10 venous segments cryopreserved for 10 months, was significantly higher than in 13 veins stored in saline for 12 hours at 4 degrees C (2.8 +/- 0.4 vs 0.4 +/- 0.1 PG ml-1mg-1min-1, respectively; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Viability of long-term cryopreserved human saphenous veins. 232 91

It was investigated whether the prostacyclin derivative Iloprost (Schering, Berlin) protects rat hepatocytes against lethal damage induced by carbon tetrachloride (CCl4) and bromobenzene (BB). Iloprost was tested in whole animal experiments (intoxication with 2 ml CCl4/kg) and with primary hepatocyte cultures (intoxication with 1.6 mM BB). Cell damage was estimated by light microscopic examination of hepatocellular morphology and by the release of hepatocellular enzymes (glutamic-pyruvic transaminase, GPT; glutamic-oxalacetic transaminase, GOT; lactic dehydrogenase, LDH) into the blood or culture medium. In both experimental set-ups, Iloprost (0.1 micrograms/kg/min in whole animal experiments and 10(-9)-10(-12) M in primary hepatocyte cultures) largely preserved normal hepatocellular morphology after intoxication. Furthermore, the toxin-induced release of hepatocellular enzymes into the blood (GOT, GPT) or into the culture medium (LDH) was reduced by 50%-70% in the presence of Iloprost. It is concluded that the prostacyclin derivative Iloprost possesses cytoprotective activity on rat hepatocytes against lethal injury by CCl4 or BB.
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PMID:Cytoprotective effect of the prostacyclin derivative iloprost against liver cell death induced by the hepatotoxins carbon tetrachloride and bromobenzene. 243 51

The effects of OKY-046, a selective thromboxane A2 (TXA2) synthetase inhibitor, and ONO-3708, a novel TXA2 receptor antagonist, on liver disease were investigated in mice. The liver injury was induced by either an injection of antibasic liver protein (BLP) antibody into DBA/2 mice that had been previously immunized with rabbit IgG or by an injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum (C. parvum) pretreated DDY mice. 1) In both injury models, clear elevation of glutamate transaminase (GOT and GPT) activity due to extensive liver parenchymal cell damage was observed; this was confirmed by significant histopathological changes in the liver. 2) Typical histopathological changes in the liver were submassive hepatocellular necrosis in the anti-BLP antibody-induced injury model and focal necrosis in the LPS-induced model. Inflammation and increased cell infiltration in portal connective tissue were observed in both cases. 3) Administration of OKY-046 (50 mg/kg) and ONO-3708 (0.5, 1.0 and 2.0 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. 4) Indomethacin inhibited the development of liver disease caused by anti-BLP antibody but not by bacterial LPS. Prostaglandin I2 inhibited the elevation of serum GOT and GPT levels and histopathological changes of the liver in the mice treated with anti-BLP antibody and showed the tendency to inhibit the development of liver injury caused by bacterial LPS.
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PMID:Effect of OKY-046 and ONO-3708 on liver injury in mice. 251 4

The effect of prostacyclin on acetaminophen-induced liver injury has been investigated in the mouse. Two structurally unrelated thromboxane synthetase inhibitors, OKY 1581 and benzyl imidazole, were also examined in order to investigate the role of the prostacyclin-thromboxane balance in the development of hepatic lesions. Whereas prostacyclin or OKY 1581 given shortly after acetaminophen prevented mortality and reduced liver necrosis, as assessed by serum ALT activity and histology, benzyl imidazole was only effective if given prior to acetaminophen. Acetaminophen overdose resulted in an enhanced prostaglandin and thromboxane generation by liver homogenates. While OKY 1581 inhibited thromboxane production by the liver homogenates, prostacyclin synthesis was increased. Pretreatment with the cyclooxygenase inhibitor indomethacin blocked both the increase in prostacyclin generation and the protective effect of OKY 1581. Benzyl imidazole inhibited the synthesis of thromboxane but did not enhance prostacyclin production. In addition, the protective effect of benzyl imidazole was unaltered by indomethacin pretreatment. Furthermore, whereas benzyl imidazole interfered with hepatic drug metabolism, as assessed by prolongation of the pentobarbitone sleeping time, prostacyclin and OKY 1581 were without activity. Prostacyclin treatment can prevent acetaminophen-induced liver necrosis in mice. Enhanced prostacyclin synthesis by the selective thromboxane synthetase inhibitor OKY 1581 also exerts a protective role in this model.
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PMID:Reduction by prostacyclin of acetaminophen-induced liver toxicity in the mouse. 328 85

The changes of the levels of LTC4, PGI2 and TXA2 in the liver tissue in SD rats with GaIN/LPS-induced acute liver injury was studied with radioimmunoassay (RIA). As a result, 12 h after the administration of GaIN/LPS, serum AST (398 +/- 37 u), ALT (565 +/- 43 u) increased (P < 0.001) and the concentration of TXA2 (12,188 +/- 588 pg/g.w.wt) in liver tissue increased significantly (P < 0.001), while the content of LTC4 (9713 +/- 3557 ng/g.w.wt) and PGI2(1748 +/- 560 pg/g.w.wt) in liver tissue were not obviously changed (P > 0.05) and the inflammatory changes of the pathological findings were observed. The improvement of serum ALT (330 +/- 168 u) (P < 0.05) and AST (273 +/- 124 u) (P < 0.05) and histopathological damage was observed after the administration of diethylcarbamazine (DEC), a LTA4 synthesis inhibitor, the liver TXA2 (12,740 +/- 699) concentration significantly increased (P < 0.001), while the levels of LTC4 (8179 +/- 1653) and PGI2 (2320 +/- 630) were not obviously changed. Serum ALT (536 +/- 74 u) and AST (416 +/- 41 u) (P > 0.05) levels and histopathology did not change with administration of indomethacin, a cyclooxygenase inhibitor, but the liver LTC4 (12,166 +/- 1327) contents increased (P < 0.05) and TXA2 (1868 +/- 791) reduced significantly (P < 0.001). The present study suggests that arachidonic acid metabolism in rats with acute liver injury are significantly abnormal. Leukotrienes and thromboxane are important inflammatory mediators in the liver injury.
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PMID:Arachidonic acid metabolism in galactosamine/endotoxin induced acute liver injury in rats. 780 4

It has been reported that vasodilatory prostaglandins have cytoprotective effects against various types of liver damage. We investigated the effects OP 2507, a stable analogue of prostaglandin I2, on carbon tetrachloride-induced liver damage in starved rats. Intraperitoneal administration of OP 2507 at 1,500 micrograms/kg lessened both an increase in serum alanine aminotransferase activity and an inhibition of starvation ketosis, both of which were induced by carbon tetrachloride. At lower doses, however, OP 2507 not only failed to ameliorate the carbon tetrachloride-induced changes, but it actually exaggerated them. Although the deterioration of carbon tetrachloride-induced liver damage by lower doses of OP 2507 was not statistically significant, it seems possible that OP 2507 has dual effects on carbon tetrachloride-induced liver damage. While none of the three agents cimetidine, reduced glutathione and deferoxamine, prevented increase in serum alanine aminotransferase activity induced with lower dose OP 2507, allopurinol had a tendency to prevent the increase, indicating that lower doses of OP 2507 may promote a reaction catalyzed by xanthine oxidase. We propose that both the co-administration of prostaglandins and other potentially hepatotoxic drugs, and the administration of prostaglandins to patients with drug-induced liver damage should be done carefully.
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PMID:Effects of OP 2507, a stable analogue of prostaglandin I2, on carbon tetrachloride-induced liver damage in starved rats. 872 10

The effect of antithrombin III (AT III) supplementation on energy status, microcirculation, cytoprotection, and prostacyclin (PGI2) production during and after a period of warm ischemia of the rat liver was investigated. AT III supplementation (250 units/kg) stimulate prostaglandin I2 (PGI2) production from 1 hour after administration, with maximal production observed at 3 hours. Ischemia was induced by occluding the hepatoduodenal ligament for 30 minutes, and experiments were continued for 60 minutes after reperfusion. The rats received AT III (250 units/kg IC) 30 minutes before induction of liver ischemia (AT III group). In the AT III group, recovery of the beta-ATP/inorganic phosphate ratio measured by 31P nuclear magnetic resonance showed significant improvement (p < 0.01), and the recovery of tissue blood flow markedly improved (p < 0.01) compared to the saline-treated group (control group). Leakages of aspartame aminotransferase, alanine aminotransferase, and lactate dehydrogenase were mitigated in the AT III group (p < 0. 05). Ultrastructural alterations of sinusoidal endothelial cells were markedly reduced in the AT III group. The PGI2 level at the end of reperfusion was significantly elevated (p < 0.01) in the AT III group compared to the control group. The results of this study indicated that pretreatment with AT III significantly improved the energy status and microcirculation, as well as histologic damage, after liver ischemia and reperfusion. One of the fundamental effects of AT III might be mediated through the production of prostacyclin.
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PMID:Protective effects of antithrombin III supplementation on warm ischemia and reperfusion injury in rat liver. 879 66

Exogenously administered prostaglandins are reported to be involved in hepatic regeneration, i.e. they hinder liver cell injury and cell-death induced by different toxic noxae. In the pertinent literature no data are available regarding the role of endogenous (tissue) prostaglandins in hepatotoxic processes. In subchronic carbon-tetrachloride intoxication (800 mg/kg twice a week, s.c., for 12 weeks) the endogenous prostacyclin level showed a transient and significant elevation signalling (similarly to the gastrointestinal tract) the process of protective mechanisms. This tenet was further strengthened by the concomitant decrease of serum ALT and AST levels. Continuing the carbon-tetrachloride treatment, finally not only the endogenous prostacyclin synthesising capacity of the liver but the hepatic cells themselves were also destroyed. According to the author's best knowledge these are the first data in the literature which try to enlighten the protective role of endogenous prostacyclin in hepatotoxic processes.
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PMID:Possible role of endogenous prostacyclin in the maintenance of hepatic integrity in rat. 957 Apr 95

The shortage of suitable organs for liver grafts is responsible for the use of marginal donors for liver transplantation (OLT). If these liver grafts function poorly initially after OLT, a supportive therapy is necessary. The purpose of this study was to evaluate the effects of prostacyclin (PGI2) on postoperative liver graft function after OLT. A total of 30 adult recipients of primary OLT were randomized to either receive PGI2 (4 ng/kg per min body weight, n = 15) or a placebo for 6 d. To evaluate regional splanchnic oxygenation a fiberoptic pulmonary-artery catheter was inserted into a hepatic vein and the difference between mixed venous oxygen content and hepatic venous oxygen content was determined (deltaO2). Measurements were performed directly after transplantation and at 6, 12, 24 and 48 h postoperatively. A significant correlation between deltaO2 and the level of transaminases (ALT/AST) was observed 24 and 48 h after transplantation (p < 0.05). PGI2 treatment induced a significant decrease in deltaO2 after 24 and 48 h after reperfusion (p < 0.05). Peak AST levels tended to be lower in the PGI2 treatment group (418 +/- 99 vs. 638 +/- 156 U/L, p < 0.1). These results suggest that administration of PGI2 after OLT improves hepatic-splanchnic oxygenation and may thereby reduce reperfusion injury after OLT.
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PMID:Administration of prostacyclin after liver transplantation: a placebo controlled randomized trial. 1069 39


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