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Glutathione, glutathione‐dependent enzymes and antioxidant status in erythrocytes from children treated with high‐dose paracetamol
Author(s) -
Kozer Eran,
Evans Sandra,
Barr Joseph,
Greenberg Revital,
Soriano Ingrid,
Bulkowstein Mordechai,
Petrov Irena,
ChenLevi Zehava,
Barzilay Bernard,
Berkovitch Matitiahu
Publication year - 2003
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2003.01723.x
Subject(s) - glutathione , glutathione peroxidase , glutathione reductase , antioxidant , superoxide dismutase , medicine , pharmacology , confidence interval , chemistry , endocrinology , gastroenterology , biochemistry , enzyme
AimTo investigate glutathione and antioxidant status changes in erythrocytes from febrile children receiving repeated supratherapeutic paracetamol doses.MethodsFifty‐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.ResultsAspartate 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 µmol gHb −1 , 95% confidence interval (CI) 2.10–4.72, and 2.15 µmol 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).ConclusionsIn 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.