The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Mode of Cell Death after Acetaminophen Overdose in Mice: Apoptosis or Oncotic Necrosis?
Abstract
Acetaminophen (AAP) overdose can cause severe liver injury and liver failure in experimental animals and humans. Recently, several authors proposed that apoptosis might be a major mechanism of cell death after AAP treatment. To address this controversial issue, we evaluated a detailed time course of liver injury after AAP (300 mg/kg) in fasted C3Heb/FeJ mice. Apoptotic hepatocytes were quantified in H&E-stained liver sections using morphologic criteria (cell shrinkage, chromatin condensation and margination, and apoptotic bodies). The number of apoptotic hepatocytes remained at baseline (0.2 +/- 0.1 cells/10 high-power fields [HPF]) up to 2 h after AAP administration. However, between 3 and 24 h, apoptotic cell death increased significantly, e.g., 6.3 +/- 0.8 cells/10 HPF at 6 h. Despite the increase in the number of hepatocytes meeting the morphological criteria of apoptosis, this cell fraction remained well below 1% of all parenchymal cells. No evidence for caspase-3 processing or increase in enzyme activity was detected at any time. These results were compared to the overall percent of necrotic cells in liver sections. Confluent areas of centrilobular necrosis were estimated to involve 40-60% of all hepatocytes between 3 and 24 h after AAP administration. These numbers correlated with the increase in plasma alanine aminotransferase activities, which reached a peak level of 5900 +/- 1350 U/l at 24 h. A similar result was obtained with higher doses of AAP and with the use of fed animals. Thus, oncotic necrosis and not apoptosis is the principal mechanism of liver-cell death after AAP overdose in vivo.
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Cites
Knight, T. R. (2001) · Toxicological Sciences · doi:10.1093/toxsci/62.2.212 · Cited by 313
Ca 2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen 1
Ray, S. D., Kamendulis, L. M., Gurule, M. W., Yorkin, R. D., & Corcoran, G. B. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.5.8462787 · Cited by 198
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Apoptosis and necroptosis in the liver: a matter of life and death
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Hanawa, N., Shinohara, M., Saberi, B., Gaarde, W. A., Han, D., & Kaplowitz, N. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708916200 · Cited by 527
C-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity
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Saito, C., Zwingmann, C., & Jaeschke, H. (2010) · Hepatology · doi:10.1002/hep.23267 · Cited by 430
Cover, C., Mansouri, A., Knight, T. R., Bajt, M. L., Lemasters, J. J., Pessayre, D., & Jaeschke, H. (2005) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.088898 · Cited by 373
Antoine, D. J., Williams, D. P., Kipar, A., Jenkins, R. E., Regan, S. L., Sathish, J. G., Kitteringham, N. R., & Park, B. K. (2009) · Toxicological Sciences · doi:10.1093/toxsci/kfp235 · Cited by 223
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Macrophages as a Cell-Based Therapy for Liver Disease
Starkey Lewis, P. J., Moroni, F., & Forbes, S. J. (2019) · Seminars in Liver Disease · doi:10.1055/s-0039-1688502 · Cited by 36
Wang, Q., Peng, X., Chen, Y., Tang, X., Qin, Y., He, M., Chen, W., & Chen, H. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.02.043 · Cited by 24
Old problem, new solutions: biomarker discovery for acetaminophen liver toxicity
Gloor, Y., Schvartz, D., & F.Samer, C. (2019) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2019.1642323 · Cited by 18
Nguyen, N. T., Umbaugh, D. S., Huang, E. L., Adelusi, O. B., Sanchez Guerrero, G., Ramachandran, A., & Jaeschke, H. (2022) · Toxicological Sciences · doi:10.1093/toxsci/kfac057 · Cited by 15
Metadata
- Authors
- Gujral, J. S.
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-06-01
- Volume
- 67
- Issue
- 2
- Pages
- 322-328
- ISSN
- 1096-0929 (ISSN-L)
- OpenAlex
- W2134586772
- Cited by
- 422
- References
- 2
- FWCI
- 11.09
- Type
- journal article
- Language
- en
- Open access
- closed
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