title: Glutathione, glutathione-dependent enzymes and antioxidant status in erythrocytes from children treated with high-dose paracetamol.
abstract: OBJECTIVE
  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 degrees 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 micromol gHb(-1), 95% confidence interval (CI) 2.10-4.72, and 2.15 micromol 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.
authors.affiliation: Emergency Department, Biochemistry Laboratory, Clinical Pharmacology and Toxicology Unit, and Division of Pediatrics, Assaf Harofeh Medical Centre, Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Kozer
authors.forename: Sandra
authors.initials: S
authors.lastname: Evans
authors.forename: Joseph
authors.initials: J
authors.lastname: Barr
authors.forename: Revital
authors.initials: R
authors.lastname: Greenberg
authors.forename: Ingrid
authors.initials: I
authors.lastname: Soriano
authors.forename: Mordechai
authors.initials: M
authors.lastname: Bulkowstein
authors.forename: Irena
authors.initials: I
authors.lastname: Petrov
authors.forename: Zehava
authors.initials: Z
authors.lastname: Chen-Levi
authors.forename: Bernard
authors.initials: B
authors.lastname: Barzilay
authors.forename: Matitiahu
authors.initials: M
authors.lastname: Berkovitch
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000975:Antioxidants / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000097:blood; D005980:Glutathione Reductase / Q000097:blood; D005982:Glutathione Transferase / Q000097:blood; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D000975:Antioxidants; D000082:Acetaminophen; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione