Glutathione status etc in erythrocytes from children treated with high-dose paracetamol = acetaminophen = Tylenol

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1: Br J Clin Pharmacol. 2003 Mar;55(3):234-40.

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Glutathione, glutathione-dependent enzymes and antioxidant

status in erythrocytes from children treated with high-dose

paracetamol.

*Kozer E*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Kozer%20E\

%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Di\

scoveryPanel.Pubmed_RVAbstractPlus>,

* S*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22%20S\

%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Di\

scoveryPanel.Pubmed_RVAbstractPlus>,

*Barr J*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Barr%20J%\

22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Dis\

coveryPanel.Pubmed_RVAbstractPlus>,

*Greenberg R*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Greenberg\

%20R%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_DiscoveryPanel.Pubmed_RVAbstractPlus>,

*Soriano I*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Soriano%2\

0I%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_\

DiscoveryPanel.Pubmed_RVAbstractPlus>,

*Bulkowstein M*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Bulkowste\

in%20M%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pub\

med_DiscoveryPanel.Pubmed_RVAbstractPlus>,

*Petrov I*

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I%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_D\

iscoveryPanel.Pubmed_RVAbstractPlus>,

*Chen-Levi Z*

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%20Z%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_DiscoveryPanel.Pubmed_RVAbstractPlus>,

*Barzilay B*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Barzilay%\

20B%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\

_DiscoveryPanel.Pubmed_RVAbstractPlus>,

*Berkovitch M*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Berkovitc\

h%20M%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubm\

ed_DiscoveryPanel.Pubmed_RVAbstractPlus>.

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.

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 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.

PMID: 12630972