Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Present package labeling for sevoflurane recommends the use of fresh gas flow rates of 2 L/min or more when delivering anesthesia with sevoflurane. This recommendation resulted from a concern about the potential nephrotoxicity of a degradation product of sevoflurane, "Compound A," produced by the action of carbon dioxide absorbents on sevoflurane. To assess the adequacy of this recommendation, we compared the nephrotoxicity of 8 h of 1.25 minimum alveolar anesthetic concentration (MAC) sevoflurane (n = 10) versus desflurane (n = 9) in fluid-restricted (i.e., nothing by mouth overnight) volunteers when the anesthetic was given in a standard circle absorber anesthetic system at 2 L/min. Subjects were tested for markers of renal injury (urinary albumin, glucose, alpha-glutathione-S-transferase [GST], and pi-GST; and serum creatinine and blood urea nitrogen [BUN]) before and 1, 2, 3, and/or 5-7 days after anesthesia. Desflurane did not produce renal injury. Rebreathing of sevoflurane produced average inspired concentrations of Compound A of 41 +/- 3 ppm (mean +/- SD). Sevoflurane was associated with transient injury to: 1) the glomerulus, as revealed by postanesthetic albuminuria; 2) the proximal tubule, as revealed by postanesthetic glucosuria and increased urinary alpha-GST; and 3) the distal tubule, as revealed by postanesthetic increased urinary pi-GST. These effects varied greatly (e.g., on postanesthesia Day 3, the 24-h albumin excretion was < 0.03 g (normal) for one volunteer; 0.03-1 g for five others; 1-2 g for two others; 2.1 g for one volunteer; and 4.4 g for another volunteer). Neither anesthetic affected serum creatinine or BUN, nor changed the ability of the kidney to concentrate urine in response to vasopressin, 5 U/70 kg subcutaneously (i.e., these measures failed to reveal the injury produced). In addition, sevoflurane, but not desflurane, caused small postanesthetic increases in serum alanine aminotransferase (ALT), suggesting mild, transient hepatic injury.
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PMID:Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers. 945 67

Subclinical disturbance in hepatocellular integrity, indicated by glutathione transferase Alpha (GSTA), has been associated with halothane, sevoflurane and propofol, but not with isoflurane anaesthesia. We anaesthetized 82 patients with isoflurane or halothane at 1 MAC for superficial surgery. GSTA concentration were measured with a sensitive time-resolved immunofluorometric assay in serum samples. GSTA concentrations increased from a baseline value of geometric mean 1.8 micrograms litre-1 (95% confidence intervals 1.4-2.2 micrograms litre-1) to a peak of 4.3 (3.3-5.7) micrograms litre-1 in the isoflurane group and from 2.1 (1.6-2.9) micrograms litre-1 to 6.2 (4.1-9.5) micrograms litre-1 in the halothane group. The change in GSTA was significant within groups but the difference between groups was not significant. Two patients exhibited an unexpectedly large increase in GSTA (peaks 370 and 620 micrograms litre-1) and a mild increase in alanine aminotransferase after halothane anaesthesia. We conclude that hepatocellular integrity was mildly disturbed after isoflurane and halothane anaesthesia but there was no difference between anaesthetics. Halothane anaesthesia may be associated with more advanced hepatocellular disturbance in some cases.
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PMID:Hepatocellular integrity during and after isoflurane and halothane anaesthesia in surgical patients. 921 37

The effects of sevoflurane and isoflurane on serum glutathione S-transferase concentrations and creatinine clearance were compared in 50 ASA I-III patients aged over 18 years undergoing body surface surgery of 1-3 h predicted duration. Patients randomly received sevoflurane (n = 24) or isoflurane (n = 26) in nitrous oxide and oxygen (FIO2 = 0.4) via a nonrebreathing system. Fluids were standardised and patient's lungs ventilated to normocapnia. Expired concentration of anaesthetic agent was adjusted to maintain systolic arterial pressure between 70 and 100% of baseline. Patients received significantly less (p < 0.05) sevoflurane (1.0 MAC-h) than isoflurane (1.5 MAC-h). Using serum glutathione S-transferase concentrations and creatinine clearance as markers of hepatic and renal function respectively, no statistically significant differences were identified between the groups.
Anaesthesia 1997 Feb
PMID:Serum glutathione S-transferase concentrations and creatinine clearance after sevoflurane anaesthesia. 905 93

We have assessed hepatocellular integrity in patients anaesthetized with desflurane or isoflurane using glutathione transferase Alpha (GSTA) as a sensitive indicator. Volatile anaesthetic was administered to 72 women at 0.7 MAC for 25 min and thereafter at 1.0 MAC. GSTA was measured with a time-resolved immunofluorometric assay in serum samples. Mild or moderate increases in GSTA were found in approximately 40% of patients immediately after anaesthesia. In the desflurane group (n = 30) the increase in GSTA concentration was from a baseline value of the geometric mean of 1.3 microgram litre-1 (95% confidence interval 0.9-1.9 microgram litre-1) to a peak of 2.6 (1.8-3.8) micrograms litre-1. The corresponding increase in the isoflurane group (n = 31) was from 1.3 (0.9-1.9) microgram litre-1 to 3.0 (2.2-4.2) micrograms litre-1. The change in GSTA concentration was significant in both groups but not between groups. No predictive factors for the increase in GSTA concentrations were found. Increased GSTA concentrations were not accompanied by increases in amino-transferases. We conclude that desflurane and isoflurane anaesthesia were associated with a mild subclinical disturbance of hepatocellular integrity.
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PMID:Changes in hepatocellular integrity during and after desflurane or isoflurane anaesthesia in patients undergoing breast surgery. 950 85

In 32 published reports in surgical patients, the preponderance of evidence from standard clinical measures of renal function (BUN and Cr) indicates the absence of renal toxicity following sevoflurane anesthesia. Studies of surgical patients receiving intermediate-duration sevoflurane with high or low fresh gas flow and long-duration sevoflurane with high fresh gas flow included sensitive measures of renal function and/or injury, which also indicate the absence of renal toxicity following sevoflurane anesthesia. Studies of surgical patients receiving long-duration sevoflurane with low fresh gas flow did not include sensitive measures. Seven studies in volunteers are not directly relevant to clinical practice but do raise the issue of whether it is important to apply sensitive measures of renal function and/or injury such as urine concentrations and/or excretion of NAG, beta 2M, alpha 1M, AAP, alpha GST, pi GST, gamma GTP, albumin, protein, and glucose and Cr clearance. Two studies of volunteers receiving prolonged sevoflurane anesthesia with fresh gas flow no greater than 2 L/min concluded that the potential for adverse renal effects of sevoflurane may exist. The other studies of volunteers did not. In 14 published reports of surgical patients in special conditions, the preponderance of evidence from standard clinical measures of renal function indicates the absence of renal toxicity. Studies with sensitive measures have been reported for some conditions where the kidney may be at increased risk (e.g., sevoflurane-induced hypotension, advanced age, and renal insufficiency and failure), are incomplete in others (e.g., hypertension and ischemic heart disease), and are missing in others (e.g., morbid obesity). Studies with sensitive measures of renal function and/or injury are also missing in an important group where the kidney may not be at increased risk--pediatric patients. Studies of other risk conditions, such as temporary ischemia, hemorrhagic hypotension, nephrotoxic antibiotics, kidney transplantation, and diabetes may provide additional information about the renal effects of sevoflurane.
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PMID:Renal effects of sevoflurane during conditions of possible increased risk. 980 93

Sevoflurane, like all currently used volatile anaesthetics, is degraded by carbon dioxide absorbents. The most significant degradant is a haloalkene known trivially as "compound A". Compound A is nephrotoxic in rats and, at higher doses, in nonhuman primates, causing proximal tubular necrosis. There has been much interest in the potential for compound A toxicity in humans. Inhaled compound A concentrations are greatest at low flow rates, high sevoflurance concentrations, warmer absorbent, barium hydroxide vs soda lime, and drier absorbent. Typical inspired compound A concentrations during low-flow and closed-circuit sevoflurane anaesthesia in humans are 8-24 and 20-32 ppm with soda lime and barium hydroxide lime, respectively. Renal effects of compound A production during sevoflurane anesthesia have been examined in surgical patients and volunteers, using standard (creatinine clearance, serum BUN and creatinine) and experimental (urine excretion of protein, glucose, NAG, GST, AAP) markers of renal function. Investigations to date in surgical patients show similar renal effects of low-flow sevoflurane, low-flow isoflurane or high-flow sevoflurane. There have been no case reports of compound A-associated renal injuryin humans. In volunteers, one study found changes in experimental but not conventional renal markers, while other investigations show no significant changes in either standard or experimental markers. The mechanism of compound A nephrotoxicity in rats appears to involve metabolism to glutathione and cysteine conjugates, and their subsequent renal uptake and metabolism by pathways that are different in rats and humans.
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PMID:[Compound A: toxicology and clinical relevance]. 989 74

The objective of this study was to elucidate whether microcystin-LR (MC-LR), a hepatotoxic blue-green algal toxin in drinking water, is carcinogenic or possesses the ability to modulate aflatoxin B1 (AFB1)-induced hepatocarcinogenicity. In a medium-term liver bioassay, male Fischer 344 rats were given a single i.p. injection of diethylnitrosamine (DEN, 200 mg/kg) followed by an i.p. injection of MC-LR for 6 weeks after 2 weeks of DEN treatment. To study the synergism between AFB1 and MC-LR, DEN-treated rats were given an i.p. injection of AFB1 (0.5 mg/kg) dissolved in dimethyl sulfoxide (DMSO) followed by MC-LR at 2 weeks after the treatment. In a separate experiment, the rats were first given AFB1 (0.5 mg/kg) and 2 weeks later an i.p. injection of 1 or 10 microg/kg of MC-LR twice a week for 6 weeks. Most rats were subjected to a two-thirds partial hepatectomy (PH) at week 3 and were killed under anesthesia at week 8. Liver sections were analyzed for glutathione S-transferase placental form (GST-P) expression, and subjected to histopathological examination for phenotypic alteration of hepatocellular foci. In rats that did not receive DEN, MC-LR did not cause a significant increase in the numbers of GST-P-positive foci, whereas AFB1 induced a slight increase in GST-P-positive foci development. In rats given DEN, MC-LR enhanced the expression of GST-P-positive foci, as did AFB1 but no synergism was observed. Histopathological analysis revealed that the area of eosinophilic foci, a biomarker for preneoplastic liver lesion, markedly increased because of MC-LR. In rats given AFB1 as an initiator, treatment with MC-LR resulted in a synergistic increase in the development of GST-P-positive foci. These results suggest that the hepatocarcinogenicities of MC-LR and AFB1 can be predicted in experimental animals with a medium-term bioassay. Furthermore, tumor promoting activity of MC-LR was demonstrated in rats treated with AFB1.
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PMID:Enhancement of glutathione S-transferase placental-form positive liver cell foci development by microcystin-LR in aflatoxin B1-initiated rats. 993 64

The purpose of this study was to investigate the influence of isoflurane and desflurane on hepatocellular function. Twenty male patients undergoing elective surgery were randomly assigned to receive either isoflurane or desflurane anaesthesia. Alpha glutathione S-transferase concentrations and aminotransferase activities were measured at induction of anaesthesia (t0), 15 min (t1), 90 min after induction (t2), end of surgery (t3) and 2 h thereafter (t4). A significant increase in alpha glutathione S-transferase concentration was observed only in the isoflurane group. Alpha glutathione S-transferase levels increased significantly from 2.3 microg.l-1 at t0 to 6.1 (1.9) microg.l-1 at t2 and to 7.8 (2.1) microg.l-1 at t3. A significant difference in alpha glutathione S-transferase concentration between the two groups was found at t2 and t3. The significant increases in alpha glutathione S-transferase concentrations in patients receiving isoflurane suggest a transient disturbance of hepatocellular function.
Anaesthesia 1999 Dec
PMID:Comparison of the effects of desflurane and isoflurane anaesthesia on hepatocellular function assessed by alpha glutathione S-transferase. 1094 85

We studied the effects of prolonged anaesthesia (4.3-7.7 h) with sevoflurane and halothane on hepatic function in 14 paediatric patients. Hepatic function was assessed using serum concentrations of liver-specific glutathione S-transferase alpha (GSTA) before and 0, 3 and 15 h after the end of anaesthesia. A transient significant increase in GSTA over baseline was observed in the sevoflurane group, but not in the halothane group, and the difference between the groups was not significant. These data suggest that, although statistically insignificant, the use of sevoflurane for prolonged anaesthesia in paediatric patients is more likely than halothane to be involved in damage to hepatic function.
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PMID:Serum glutathione S-transferase alpha as a measure of hepatocellular function following prolonged anaesthesia with sevoflurane and halothane in paediatric patients. 1088 96

The effect of propofol on the hepatic and extrahepatic conjugation enzyme systems was assessed in vitro using microsomal and cytosolic preparations of human liver, hamster kidney, lung and gut. The functional activities of phase-II enzymes, including uridine diphosphate-glucuronosyltransferase (UDPGT), glutathione S-transferase (GST) and N-acetyltransferase (NAT) were evaluated in the presence of various concentrations of propofol (0.05-1.0 mmol litre-1), using 1-naphthol, 1-chloro-2,4-dinitrobenzene and p-aminobenzoic acid as substrates respectively. Propofol produced concentration-dependent inhibition of UDPGT activity in human liver microsomes. Propofol did not produce significant inhibition of human hepatic GST activity at concentrations below 1.0 mmol litre-1. In contrast, NAT activity was unaffected by propofol 0.05-1.0 mmol litre-1 in human liver cytosolic preparations. In extrahepatic tissues, hamster renal and intestinal UDPGT activities were significantly inhibited by propofol at 0.25-1.0 mmol litre-1. In these tissues, GST and NAT were unaffected by propofol at 1.0 mmol litre-1. Propofol produced differential inhibition of human liver and hamster extrahepatic conjugation enzymes as a result of different substrate and tissue specificities. The potential interference of the metabolic profile of phase-II enzymes as a result of inhibition by propofol (especially of UDPGT and GST) should be considered when using propofol with other drugs for anaesthesia.
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PMID:Effects of propofol on functional activities of hepatic and extrahepatic conjugation enzyme systems. 1089 55


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