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)

A severe compression craniocerebral trauma was induced in rats under short-term halothane anesthesia. The activity of pyruvate and 2-oxoglutarate dehydrogenase complexes reduced significantly in the tissue of the damaged hemisphere, ALT activity increased sharply, AST activity grew slowly, the production of GABA in the glutamate decarboxylase reaction was slightly inhibited and its utilization in the GABA transaminase reaction was clearly accelerated. The GABA level in the nerve tissue showed a tendency to reduce, while the glutamate level had a tendency to increase. The observed changes are evidence that the inclusion of the GABA skeleton in the reaction of further oxidation intensifies, which may be of significance in compensation of the transport of the energetically oxidizing succinate and, possibly, in the formation of endogenous GABA possessing a stress-relieving effect.
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PMID:[The compensatory function of a GABA shunt in brain energy metabolism in measured craniocerebral trauma in rats]. 290 62

The potential hepatotoxic activity of isoflurane, a volatile anesthetic agent recently introduced in Italy, has been investigated by the Authors in the present study. Hepatic markers blood level (GPT, gamma GT, alkaline phosphatase and albumin) have been checked preoperatively and at day 1 and 4 postoperatively in a group of 35 patients who underwent general anesthesia for plastic surgery operations by means of isoflurane. As control group 32 patients were tested, treated with general anesthesia for the same type of surgery by means of halotane. The Authors conclude that isoflurane, according to the data obtained from present study, cannot be, at the moment, considered hepatotoxic.
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PMID:[Hepatic injury and halogenated anesthetics: preliminary clinical experience]. 293 32

Serial physiological responses were examined for 150 min from captive collared peccaries during immobilization with ketamine hydrochloride. Rectal temperatures decreased significantly (P less than 0.01) during anesthesia. Serum concentrations of total proteins, albumin, cholesterol, alanine aminotransferase, and calcium declined significantly (P less than 0.05) during the first 45 min post-immobilization before stabilizing. Concentrations of lactate dehydrogenase and alkaline phosphatase in sera showed similar but nonsignificant (P greater than 0.05) trends. Inorganic phosphorus and aspartate aminotransferase concentrations increased significantly (P less than 0.05) throughout the trial. Concentrations of serum glucose and glucocorticoid during the immobilization period were highly variable between individuals. Serum electrolytes, urea nitrogen, creatinine, gammaglutamyl transferase and progesterone were not significantly (P greater than 0.05) affected by immobilization. Elevations in serum testosterone were noted. Results indicated appropriate sampling times relative to immobilization for assay of particular serum biochemicals and steroid hormones during investigations of the physiology of the collared peccary.
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PMID:Endocrine and metabolic responses of the collared peccary (Tayassu tajacu) to immobilization with ketamine hydrochloride. 300 72

In order to evaluate the clinical implication of experimental studies on halothane-induced liver damage in phenobarbital-treated rats, we studied the clinical records of 315 consecutive patients who underwent brain surgery with halothane anesthesia. After exclusion of subjects with a history of alcoholism or antecedent chronic liver disease, clinical data of 279 patients with normal preoperative transaminase activities were analyzed. The incidence of halothane-induced liver injury was significantly higher in the subjects given phenobarbital than in those with no phenobarbital medication (7/100 vs. 1/179, p less than 0.01). To determine if other anticonvulsant compounds can influence halothane-induced liver injury, rats were pretreated with diphenylhydantoin or valproic acid prior to exposure to halothane under hypoxic conditions for comparison with phenobarbital. The degree of halothane hepatotoxicity assessed from ALT activities and morphological alterations was of the decreasing order of phenobarbital greater than controls = diphenylhydantoin greater than valproic acid, and a similar order was observed in the extent of reductive metabolism of halothane. These results indicate that patients pretreated with phenobarbital may be at a greater risk of halothane-induced liver damage, and that treatment with valproic acid and diphenylhydantoin lead to the production of toxic intermediates of halothane to a lesser extent than treatment with phenobarbital does.
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PMID:Effects of anticonvulsant agents on halothane-induced liver injury in human subjects and experimental animals. 309 58

This study demonstrates that the exposure of phenobarbitone-treated rats to halothane at an oxygen concentration of either 10% or 14% results in marked decreases in cytochrome P-450 content and aminopyrine demethylase activity in animals sacrificed from 1 to 48 hr post-exposure. The alterations observed in the hepatic mixed function oxidase system were accompanied by increases in serum alanine aminotransferase (ALT), ornithine carbamyl transferase (OCT) and changes in liver pathology. However, the minor changes in cytochrome P-450 content and aminopyrine demethylase activity observed following exposure of enzyme-induced rats to halothane under normoxic conditions (i.e. 21% oxygen) were not of a sufficient magnitude to lead to hepatic cell necrosis. Halothane administration in the absence of phenobarbitone pretreatment (i.e. 21% oxygen) or during hypoxia alone (i.e. either 10% or 14% oxygen) did not result in any systematic changes in the parameters assayed. The results suggest that cytochrome P-450 may catalyse its own inactivation by virtue of greater free radical production under conditions which favour the non-oxygen dependent metabolism of halothane. The impairment in microsomal function as evidenced by decreases in cytochrome P-450 and aminopyrine demethylase activity are considered to occur as a primary consequence of the reductive metabolism of halothane. Data are presented which support the concept of the initiation of hepatic damage occurring during the period of anaesthesia with halothane.
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PMID:Changes in rat hepatic microsomal mixed function oxidase activity following exposure to halothane under various oxygen concentrations. 310 40

Five hundred seventy-six consecutive patients from the surgical, obstetrical, and medical services who had received transfusions of volunteer blood were followed-up at regular intervals for 6 mo. Fifty-three (9.2%) developed acute posttransfusion non A, non B hepatitis. Forty-seven (89%) had an incubation period between 2 and 8 wk. The frequency was not related to the age or sex of the patient, the indications for transfusion, the type of surgery, anesthesia, the presence of perioperative hypotension, or the number of units of blood transfused. There were no cases of fulminant hepatitis. Nineteen of the 53 patients (36%) with acute posttransfusion hepatitis progressed to chronic hepatitis. Development of chronic hepatitis was not related to the age or sex of the patient, the incubation period of the preceding acute hepatitis, the presence of shock or malignancy, or the number of units of blood transfused. Patients with higher levels of alanine aminotransferase during the acute hepatitis were more prone to develop chronic hepatitis. The finding of 9.2% of transfusion-related hepatitis in recipients of hepatitis B surface antigen-screened blood from volunteer donors underscores the potential sequelae of blood transfusion, especially as a source of contribution to the pool of chronic liver disease.
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PMID:Posttransfusion hepatitis in Toronto, Canada. 313 69

Hepatic damage was induced in phenobarbitone pretreated male Fischer 344 rats by the administration of 1% halothane in 14% oxygen for either 1 or 2 hours. Ethane production during the exposure period was not significantly different between the halothane and non-halothane exposed groups. Animals were sacrificed 1, 2, 6 and 24 hrs from commencement of anaesthesia and the hepatic microsomal fraction analyzed for diene conjugates, lipid hydroperoxides, total lipid content and fatty acid composition. Animals exposed to halothane and sacrificed at 2 and 24 hrs had significantly elevated levels of diene conjugates (P less than 0.05), while lipid hydroperoxide concentration and serum alanine aminotransferase increased in only those animals sacrificed at 24 hrs. Alterations in total lipid content and hepatic microsomal fatty acid composition were not observed in animals sacrificed after 1 and 2 hrs. A significant reduction in total lipid and arachidonic acid content occurred only in those animals sacrificed 24 hrs after exposure, however a concomitant increase in the saturated fatty acid fraction was not observed. It is proposed that alterations in fatty acid composition in vivo and evidence of lipid peroxidation occur as a result of cell death rather than an initiating event in halothane induced hepatic necrosis in rats.
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PMID:Halothane induced hepatic necrosis in rats: the role of in vivo lipid peroxidation. 323 93

Administration of caffeine (CAF) to mice as early as 6 hr prior to injection of a hepatotoxic but nonlethal dose of acetaminophen (ACM) significantly antagonized the hepatotoxic action of ACM as judged by serum levels of alanine aminotransferase (ALT) activity. Administration of CAF after ACM produced complete antagonism only when CAF was given no later than 1 hr after ACM. Administration of CAF daily for 3 days prior to injection of ACM enhanced ACM toxicity markedly, but little or no toxicity ensued when CAF-pretreated mice received ACM followed immediately by CAF. The four primary metabolites of CAF, 1,3-dimethylxanthine (theophylline), 3,7-dimethylxanthine (theobromine), 1,7-dimethylxanthine (paraxanthine), and 1,3,7-trimethyluric acid were effective and virtually complete antagonists of ACM-induced hepatotoxicity when given immediately after ACM, as were the secondary metabolites, 1-methylxanthine and 1,3-dimethyluric acid. Allopurinol, which reduces theophylline clearance, increases the rate of oxidative N-demethylation of theophylline to 1-methylxanthine, and inhibits conversion of 1-methylxanthine to 1-methyluric acid, was also a dose-dependent antagonist of ACM-induced hepatotoxicity. The hepatotoxic response of mice to ACM is exaggerated by a brief period of diethyl ether anesthesia; CAF given immediately after ACM to previously anesthetized mice suppressed this response and maintained serum ALT levels at control values. It is suggested that CAF and its primary metabolites compete with ACM for biotransformation by the cytochrome P-450 mixed function oxidase system, thereby reducing the rate of formation of the hepatotoxic ACM metabolite.
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PMID:Interaction of caffeine with acetaminophen in mice: schedule dependency of the antagonism by caffeine of acetaminophen hepatotoxicity and the effects of caffeine metabolites, allopurinol, and diethyl ether. 336 19

Reductive metabolism of halothane was measured after acute liver injury induced by galactosamine (1.0 g/kg, IP) in rats. On the seventh day of liver injury, when previously elevated serum alanine aminotransferase levels had returned to near normal range, anaerobic release of fluoride from halothane by hepatic microsomes, which appears to reflect the reductive pathway of halothane metabolism, was still remarkably decreased (1.36 +/- 0.56 nmol/mg protein/h vs 5.88 +/- 0.58 in controls, P less than 0.001). In another set of experiments, rats (n = 8) given galactosamine 7 days earlier and saline-treated control rats were given halothane anesthesia (1.0%) under mildly hypoxic conditions (F1O2 0.14). In saline controls, halothane anesthesia resulted in a mild but statistically significant increase in serum alanine aminotransferase levels (32 +/- 4 vs 59 +/- 6 U/ml, P less than 0.001). In contrast, serum levels of this enzyme were not changed by halothane anesthesia in galactosamine-treated rats (45 +/- 3 vs 49 +/- 4 U/ml). Although care should be taken in extrapolating the importance of these animal data to humans, the results of this study suggest that halothane hepatotoxicity can be attenuated in the presence of minor liver injury as a result of decreased hepatic biotransformation of the anesthetic. The data support the view that halothane anesthesia is not necessarily contraindicated in subjects with impaired liver function.
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PMID:Halothane hepatotoxicity and reductive metabolism of halothane in acute experimental liver injury in rats. 336 63

In a randomized prospective controlled study in humans, the metabolism and hepatic effects of a single administration of halothane were compared with enflurane and meperidine. Pre- and postoperative antipyrine pharmacokinetics, intraoperative indocyanine green clearance, liver histology, and postoperative liver function tests were determined in 24 patients undergoing abdominal surgery who were randomly allocated to receive either halothane (0.5%, group I), enflurane (0.8%, group II), or meperidine (group III) as a supplement to a common basal anesthetic regimen consisting of thiopental, nitrous oxide/oxygen/muscle relaxant. In addition, end-tidal concentrations of the volatile reductive metabolites of halothane, chlorodifluoroethylene (CDF), and chlorotrifluoroethane (CTF) were determined in group I patients and serum and urinary inorganic fluoride were determined in both group I and II patients. Indocyanine green clearance was measured before anesthesia (stage I), during basal anesthesia (stage II), in the presence of surgical stimuli (stage III), and after introduction of the selected anesthetic agent (stage IV). CDF and CTF were detectable within 20 min of the start of halothane anesthesia in every patient receiving halothane. Peak serum fluoride concentrations occurred at 2 and 24 hr in the enflurane and halothane groups, respectively, whereas urinary fluoride excretion was elevated postanesthesia in the enflurane group only. There was no difference between the pre- and postoperative disposition of antipyrine in group II or III, but after anesthesia, antipyrine clearance was significantly decreased (P less than 0.02) and plasma half-life increased (P less than 0.05) in group I patients (halothane). Concentrations of serum alanine aminotransferase (ALT) and bilirubin were significantly elevated (P less than 0.5) postoperatively in groups I and II but unchanged from preoperative values in group III patients. Three of the 24 liver biopsies taken at the end of stage IV showed several foci of acute liver cell necrosis; of these, two patients were from group I and one from group II. There were no significant differences in liver cell morphology (P greater than 0.5) in biopsies taken at the end of stage IV compared with biopsies at the end of stage III, from groups I and II. The results of this study show that reductive metabolism of halothane occurs routinely in patients undergoing halothane anesthesia under conditions of normoxia. This may be the cause of the changes in antipyrine clearance after halothane anesthesia.
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PMID:A randomized prospective controlled study of the metabolism and hepatotoxicity of halothane in humans. 356 92


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