Novel mechanisms of protection against acetaminophen hepatotoxicity in mice by glutathione and N-acetylcysteine†
Version of Record online: 4 SEP 2009
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 51, Issue 1, pages 246–254, January 2010
How to Cite
Saito, C., Zwingmann, C. and Jaeschke, H. (2010), Novel mechanisms of protection against acetaminophen hepatotoxicity in mice by glutathione and N-acetylcysteine. Hepatology, 51: 246–254. doi: 10.1002/hep.23267
Potential conflict of interest: Nothing to report.
- Issue online: 23 DEC 2009
- Version of Record online: 4 SEP 2009
- Accepted manuscript online: 4 SEP 2009 12:00AM EST
- Manuscript Accepted: 26 AUG 2009
- Manuscript Received: 8 FEB 2009
- National Institutes of Health. Grant Numbers: R01 DK070195, R01 AA12916
- National Center for Research Resources. Grant Numbers: P20 RR016475, P20 RR 021940
Additional Supporting Information may be found in the online version of this article.
|HEP_23267_sm_supptext.doc||34K||Supplementary Materials and Methods|
|HEP_23267_sm_suppfig1.tif||22105K||Supplemental Figure 1: Histological assessment of liver injury (hematoxilin & eosin, H&E) in control animals or mice treated with 300 mg/kg acetaminophen (APAP) for 6 h. Some of the animals received additionally 10 ml/kg saline, 0.65 mmol/kg GSH or 0.65 mmol/kg N-acetylcysteine (NAC) iv 1.5 h after APAP. The representative pictures show extensive centrilobular necrosis as indicated by the loss of basophilic staining, vacuolization, cell swelling and karyolysis in APAP-treated animals. Both, GSH and NAC treatment improved the area of necrosis with GSH being more effective than NAC. (x200 for all panels)|
|HEP_23267_sm_suppfig2.tif||11749K||Supplemental Figure 2: Concentrations of 13C-labelled [4,5-13C]glutamate and the Krebs cycle intermediate [2,3-13C]succinate (nmol/g wet weight), as calculated from their resonances in 1H- and 13C-NMR spectra of liver extracts. The mice were treated with 300 mg/kg APAP and some subsequently received additionally 10 ml/kg saline, 0.65 mmol/kg N-acetylcysteine (l-NAC), 1.95 mmol/kg NAC (h-NAC), a mixture of 3 amino acids (0.65 mmol/kg of glycine, glutamic acid and NAC) (3AS) or a mixture of 2 amino acids (0.98 mmol/kg glycine and glutamic acid) (2AS) iv 1.5 h after APAP. Data represent means ± SE of n = 5 animals per group. *P<0.05 (compared to controls)|
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