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Aim To investigate glutathione and antioxidant status changes in erythrocytes from febrile children receiving repeated supratherapeutic paracetamol doses. Methods Fifty-one children aged 2 months to 10 years participated in the study. Three groups were studied: group 1 ( n = 24) included afebrile children who did not receive paracetamol; and groups 2 ( n = 13) and 3 ( n = 14) included children who had fever above 38.5 ∞ C for more than 72 h. Patients in group 2 received paracetamol at a dose of 50 ± 15 (30-75) mg kg -1 day -1 and those in group 3 received paracetamol above the recommended therapeutic dose, ie 107 ± 28 (80-180) mg kg -1 day -1 . A blood sample was taken for the measurement of liver transaminases, gammaglutamil transferase (GGT), reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), superoxide dismutase (SOD) and antioxidant status. Results Aspartate aminotransferase activity in group 3 was higher than in the other groups ( P = 0.027). GSH, SOD and antioxidant status were significantly lower in group 3 compared with groups 1 and 2 (mean differences: for GSH 3.41 m mol gHb -1 , 95% confidence interval (CI) 2.10-4.72, and 2.15 m mol gHb -1 , 95% CI 0.65-3.65, respectively; for SOD 856 U min -1 gHb -1 , 95% CI 397-1316, and 556 U min -1 gHb -1 , 95% CI 30-1082, respectively; and for antioxidant status 0.83 mmol l -1 plasma, 95% CI 0.30-1.36, and 0.63 mmol l -1 plasma, 95% CI 0.02-1.24, respectively). GR activity was significantly lower in groups 3 and 2 in comparison with group 1 (mean differences 3.44 U min -1 gHb -1 , 95% CI 0.63-6.25, and 5.64 U min -1 gHb -1 , 95% CI 2.90-8.38, respectively). Using multiple regression analysis, paracetamol dose was found to be the only independent variable affecting GR, GST and SOD activities ( P = 0.007, 0.003 and 0.008, respectively). Conclusions In febrile children, treatment with repeated supratherapeutic doses of paracetamol is associated with reduced antioxidant status and erythrocyte glutathione concentrations. These significant changes may indicate an increased risk for hepatotoxicity and liver damage.

ObjectiveIncreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels were noted incidentally after a laparoscopic cholecystectomy. The percentage in which such elevation occurs and its clinical significance in the absence of bile duct injury were investigated. Summary Background DataBile duct injury is the most feared complication of laparoscopic cholecystectomy. Some laboratory tests may be indicative of this complication, such as increases in liver enzyme (AST, ALT, and alkaline phosphatase [ALP]) and bilirubin. These parameters have not been investigated in patients who had laparoscopic cholecystectomy and in whom no damage to the bile duct was noted. MethodsSixty-seven patients with normal results of preoperative liver function test were entered into the study. Blood was collected 24 hours after laparoscopic cholecystectomy, and AST, ALT, ALP, and bilirubin levels were measured. ResultsA mean 1.8-fold increase in AST occurred in 73% of patients; 82% showed a 2.2-fold increase in ALT. A statistically nonsignificant increase was noted in 53% of patients (ALP remained within normal limits), and in 14% of patients bilirubin levels were increased (they were primarily of the unconjugated type). ConclusionsIn many patients a significant increase in AST and ALT levels occurred after laparoscopic cholecystectomy, but they returned to normal values within 72 hours. The cause of this is unclear, and these elevations appear to have no clinical significance. 362

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