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 present study extends previous reports of hepatic damage 24 h after halothane anaesthesia in the phenobarbitone pretreated hypoxic rat model by fully characterizing the lesion during the time course of its onset and recovery. Phenobarbitone treated animals exposed to halothane (1% for 2 h in 14% inspired oxygen) were killed 1, 2, 4, 6, 12 and 24 h and 2, 3, 5, 10, 15 and 30 days after commencement of the anaesthetic period. Blood was collected 1 day before the administration of halothane and at the time of killing for determination of serum alanine aminotransferase (ALT), a biochemical index of hepatic damage. Liver tissue was obtained immediately at post-mortem for histological examination. Serum ALT was increased at the end of the anaesthetic period, i.e. 2 h, with peak levels occurring at 12-24 h and remaining elevated for 3 days after exposure. Minor changes in liver histology were evident at 2 h in 50% of the animals and by 6 h all animals had mild hepatic injury. The extent of the necrosis was maximal at 24 h and this was sustained until 3 days. By 5 days after exposure minimal evidence of liver damage was observed and animals killed at 30 days had morphologically normal livers. Elevation of serum ALT or changes in liver histology were not observed in other treatment groups. The early onset of damage at 2-6 h is in keeping with direct hepatotoxicity associated with the biotransformation of halothane.
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PMID:Halothane hepatitis in an animal model: time course of hepatic damage. 368 69

Acetaminophen (Tylenol) is a widely used analgesic/antipyretic drug which is enzymatically bioactivated, or toxified, by the cytochromes P-450 to a hepatotoxic reactive intermediary metabolite. Brief general anesthesia with diethyl ether has been shown to inhibit both the toxifying cytochromes P-450 and enzymatic glucuronidation, the latter constituting up to 60% of acetaminophen elimination via a nontoxifying pathway. Thus ether potentially could produce a temporally differentiated inhibition of bioactivating and "detoxifying" pathways, resulting in an enhancement of acetaminophen hepatotoxicity if the balance favored bioactivation. To evaluate this possibility, separate groups of male NIH strain mice were treated with acetaminophen at different times after 5 min of anesthesia with ether. Ether produced a 40-fold enhancement in acetaminophen hepatotoxicity as determined by plasma glutamic-pyruvic transaminase (GPT) concentrations. This toxicologic enhancement was observed only if acetaminophen administration was delayed, with a maximal enhancement when acetaminophen was given 6 hr after ether, and no effect with a delay of 16 hr. Similar studies in male CD-1 mice were carried out using halothane (Fluothane) as the general anesthetic given either over 5 min or over 1 hr. While halothane given over 5 min had no effect, a 1 hr anesthetic duration produced a 10-fold increase in acetaminophen hepatotoxicity as determined by peak GPT concentration, with no observed hepatotoxicity in the halothane controls. Toxicologic enhancement occurred only with delayed administration of acetaminophen; however, the maximal enhancement observed with a 6-hr delay was still evident with a 12-hr delay. Conversely, inhibition of acetaminophen hepatotoxicity was observed if acetaminophen was given either 2 hr or 18 hr after halothane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Delayed enhancement of acetaminophen hepatotoxicity by general anesthesia using diethyl ether or halothane. 369 20

The hepatotoxicity of acetaminophen is thought to be dependent upon its enzymatic bioactivation to a reactive intermediary metabolite which binds covalently to essential cellular macromolecules, thereby causing cellular death. Traditional in vivo methods using smaller mammals are mechanistically restrictive in that measures of hepatotoxicity, such as plasma glutamic-pyruvic transaminase (GPT), and chemical covalent binding to hepatocellular protein are performed at different times in separate groups of animals. We developed a microanalytical technique which allowed repetitive plasma GPT sampling from individual mice, followed by delayed determination of covalent binding in the same mouse 36 hr after acetaminophen administration. Diethyl ether anesthesia was used to enhance acetaminophen hepatotoxicity. The repetitive sampling technique permitted an accurate determination of the peak GPT concentration, which exhibited a marked interanimal variability in the time of occurrence. Individual peak GPT concentrations correlated with the respective covalent binding of acetaminophen in each mouse (r = 0.82, p less than 0.05), while the traditional method using a fixed sampling time (24 hr) failed to correlate (r = 0.50, p greater than 0.05). Ether produced a 39-fold enhancement in the severity of acetaminophen hepatotoxicity; however, a single, fixed-time sample taken at either 12 or 24 hr produced a substantial and inconsistent over- or underestimate of this toxicologic enhancement. This study shows that chemical hepatotoxicity as reflected by plasma GPT concentration cannot be quantified accurately by a single blood sample obtained from a given animal, regardless of the chosen sampling time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Murine acetaminophen hepatotoxicity: temporal interanimal variability in plasma glutamic-pyruvic transaminase profiles and relation to in vivo chemical covalent binding. 373 68

Rats which had approximately 25-30% of their calculated blood volume removed were exposed to halothane (1%) or enflurane (2%) in 33% oxygen for 30 min. Hepatic function was evaluated by determining, at various time intervals, serum activities of glutamic-oxalacetic and glutamic-pyruvic transaminase, acid phosphatase and gamma-glutamyl-transpeptidase. In this model serum enzyme activities and animal mortality were significantly increased when hypovolemic hypotension was induced during halothane anaesthesia. The same events did not occur in bleeding animals anaesthetized with enflurane. The marked disparity in hepatic dysfunction and mortality between halothane and enflurane-anaesthetized rats during hypovolemic hypotension may be explained by the more pronounced decrease of oxygen available for the liver and production of reductive toxic intermediates in animals exposed to halothane.
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PMID:Liver function following hypovolemic hypotension in rats anaesthetized with halothane or enflurane. 379 49

The effects of ketamine anesthesia (15 mg/kg body weight) on hematological and serum biochemical values were examined in six female cynomolgus monkeys (Macaca fascicularis) who were born in the wild. As control, another six female cynomolgus monkeys of the same origin were injected with physiological saline. The white blood cell count, total protein concentration, albumin concentration and calcium concentration decreased after the injection of ketamine, whereas the red blood cell count, hematocrit value, hemoglobin concentration, total cholesterol concentration, free cholesterol concentration, triglyceride concentration, transaminase activities (GOT, GPT) and alkaline phosphatase activity were not affected. A transient increase of the serum glucose level was observed within 10 minutes after ketamine injection. The relationship between these effects of ketamine anesthesia and serum cortisol levels measured by radioimmunoassay was discussed.
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PMID:[The effects of ketamine anesthesia on hematological and serum biochemical values in female cynomolgus monkeys (Macaca fascicularis)]. 380 31

In a prospective study comprising 2609 consecutive surgical patients, of whom 1166 were anesthetized with halothane, four cases of hepatitis were encountered. The incidence of hepatitis among those who received halothane was 1:292 in our material. The high incidence may be explained by the recognition of milder forms of hepatitis and by the selection of the series (over 40 years). Serum alanine aminotransferase should be investigated in all patients with postoperative pyrexia of unknown origin if mild forms of halothane hepatitis are to be discovered. The patient's history should be carefully examined for previous postoperative pyrexia of unknown origin following halothane anesthesia, in which case other anesthetics should be chosen.
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PMID:Halothane hepatitis in a prospective study of postoperative complications. 381 96

The measurement of plasma glutathione S-transferase (GST) concentrations have been used to assess the changes in hepatocellular integrity which occur following general anaesthesia. Of 20 selected patients, who received halothane for minor urological procedures, 16 showed a small transient rise in GST between 1 h and 3 h after anaesthesia. Similar changes were also observed in 8 consecutive patients who received halothane for various operative procedures. In 3 of these 28 patients a marked secondary rise in plasma GST was observed 24 h after anaesthesia. No significant changes in ALT were observed in either of the groups of patients. These data indicate two possible phases of hepatotoxicity following halothane administration which results in a transient impairment in hepatocellular integrity in the majority of patients who undergo anaesthesia with this agent.
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PMID:Impaired hepatocellular integrity during general anaesthesia, as assessed by measurement of plasma glutathione S-transferase. 381 53

Changes in three recognized liver function tests are reported following the use of propofol in 30 fit, unpremedicated women in whom propofol was used as the main anaesthetic agent. Doses of 140 to 330 mg were given, together with nitrous oxide and oxygen. All patients were undergoing minor gynaecological operations and all conformed to Grade 1 physical status of American Society of Anesthesiologists Classification. In none of these patients was there hypoxia or hypercarbia at any time during or following anaesthesia and none of the patients received any other drugs until completion of the study. No significant changes in liver enzymes (aspartate transaminase and alanine transaminase) or in serum alkaline phosphatase were detected.
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PMID:Changes in liver function tests after propofol ('Diprivan'). 387 86

Halothane anesthesia (1%) administered in 21% oxygen for 4 hr to an outbred strain of guinea pig in the absence of enzyme induction resulted in liver damage in 40 of the 65 animals studied. Necrosis was either confluent around the central veins or in scattered foci throughout the lobules. Damage was present on the second and third days after anesthesia. By day 7 the livers had recovered, evidenced by lack of histological changes and normal serum alanine aminotransferase activity. Administration of halothane in 14 or 80% inspired oxygen did not alter the extent or incidence of liver damage. Major end-metabolites of halothane biotransformation (2-chloro-1,1-difluoroethylene, 2-chloro-1,1,1-trifluoroethane, inorganic fluoride and trifluoroacetic acid) were identified at each oxygen concentration. The metabolic inhibitor SKF-525A significantly decreased the amounts of the volatile metabolites 2-chloro-1,1,1-trifluoroethane and 2-chloro-1,1-difluoroethylene. SKF-525A also decreased the incidence and severity of hepatic damage. Both halothane (1%) and isoflurane (1.1%) anesthesia caused similar reductions in mean arterial blood pressure. However, in contrast to halothane, isoflurane was not hepatotoxic. The results indicate that liver necrosis is unlikely to be caused by anesthesia per se, but rather by hepatotoxic metabolites of halothane. This model offers the opportunity to study the pathogenesis of halothane hepatotoxicity after the administration of halothane alone.
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PMID:Guinea-pig model of halothane-associated hepatotoxicity in the absence of enzyme induction and hypoxia. 397 29

Anaesthesia was induced in 24 horses with xylazine and ketamine and maintained with halothane (12 cases) or enflurane (12 cases) in oxygen. Pulse rate, arterial blood pressure, arterial blood gas values, respiratory rate and tidal volume were measured at regular intervals during anaesthesia. Serial venous blood samples were taken for assay of glucose, urea, haemoglobin, packed cell volume, gamma glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase and creatine kinase. Operating conditions and the horses' behaviour in the recovery period were also recorded. In the case of the group of horses receiving enflurane, difficulty was experienced maintaining anaesthesia deep enough for surgery. This group also displayed greater respiratory depression. There were no significant differences between arterial blood pressure values, or any of the haematological or biochemical parameters recorded in each group. Recovery from anaesthesia was significantly faster in horses receiving enflurane but less smooth. It was concluded that, although enflurane appeared to be safe in the horse, the respiratory depression and the unpleasant recovery did not make it a desirable alternative to halothane.
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PMID:Clinical anaesthesia in the horse: comparison of enflurane and halothane. 397 74


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