Peroxynitrite formation and sinusoidal endothelial cell injury during acetaminophen-induced hepatotoxicity in mice

Persistent Link:
http://hdl.handle.net/10150/610125
Title:
Peroxynitrite formation and sinusoidal endothelial cell injury during acetaminophen-induced hepatotoxicity in mice
Author:
Knight, Tamara; Jaeschke, Hartmut
Affiliation:
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA; Liver Research Institute, University of Arizona College of Medicine, Room 6309, 1501 N. Campbell Avenue, Arizona 85724, USA
Issue Date:
2004
Publisher:
BioMed Central
Citation:
Comparative Hepatology 2004, 3(Suppl 1):S46 http://www.comparative-hepatology.com/content/3/S1/S46
Journal:
Comparative Hepatology
Rights:
©  Knight and Jaeschke; licensee BioMed Central Ltd 2004
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
INTRODUCTION:Vascular injury and accumulation of red blood cells in the space of Disse (hemorrhage) is a characteristic feature of acetaminophen hepatotoxicity. However, the mechanism of nonparenchymal cell injury is unclear. Therefore, the objective was to investigate if either Kupffer cells or intracellular events in endothelial cells are responsible for the cell damage.RESULTS:Acetaminophen treatment (300 mg/kg) caused vascular nitrotyrosine staining within 1 h. Vascular injury (hemorrhage) occurred between 2 and 4 h. This paralleled the time course of parenchymal cell injury as shown by the increase in plasma alanine aminotransferase activities. Inactivation of Kupffer cells by gadolinium chloride (10 mg/kg) had no significant effect on vascular nitrotyrosine staining, hemorrhage or parenchymal cell injury. In contrast, treatment with allopurinol (100 mg/kg), which prevented mitochondrial injury in hepatocytes, strongly attenuated vascular nitrotyrosine staining and injury.CONCLUSIONS:Our data do not support the hypothesis that acetaminophen-induced superoxide release leading to vascular peroxynitrite formation and endothelial cell injury is caused by activated Kupffer cells. In contrast, the protective effect of allopurinol treatment suggests that, similar to the mechanism in parenchymal cells, mitochondrial oxidant stress and peroxynitrite formation in sinusoidal endothelial cells may be critical for vascular injury after acetaminophen overdose.
EISSN:
1476-5926
DOI:
10.1186/1476-5926-2-S1-S46
Version:
Final published version
Additional Links:
http://www.comparative-hepatology.com/content/3/S1/S46

Full metadata record

DC FieldValue Language
dc.contributor.authorKnight, Tamaraen
dc.contributor.authorJaeschke, Hartmuten
dc.date.accessioned2016-05-20T08:59:08Z-
dc.date.available2016-05-20T08:59:08Z-
dc.date.issued2004en
dc.identifier.citationComparative Hepatology 2004, 3(Suppl 1):S46 http://www.comparative-hepatology.com/content/3/S1/S46en
dc.identifier.doi10.1186/1476-5926-2-S1-S46en
dc.identifier.urihttp://hdl.handle.net/10150/610125-
dc.description.abstractINTRODUCTION:Vascular injury and accumulation of red blood cells in the space of Disse (hemorrhage) is a characteristic feature of acetaminophen hepatotoxicity. However, the mechanism of nonparenchymal cell injury is unclear. Therefore, the objective was to investigate if either Kupffer cells or intracellular events in endothelial cells are responsible for the cell damage.RESULTS:Acetaminophen treatment (300 mg/kg) caused vascular nitrotyrosine staining within 1 h. Vascular injury (hemorrhage) occurred between 2 and 4 h. This paralleled the time course of parenchymal cell injury as shown by the increase in plasma alanine aminotransferase activities. Inactivation of Kupffer cells by gadolinium chloride (10 mg/kg) had no significant effect on vascular nitrotyrosine staining, hemorrhage or parenchymal cell injury. In contrast, treatment with allopurinol (100 mg/kg), which prevented mitochondrial injury in hepatocytes, strongly attenuated vascular nitrotyrosine staining and injury.CONCLUSIONS:Our data do not support the hypothesis that acetaminophen-induced superoxide release leading to vascular peroxynitrite formation and endothelial cell injury is caused by activated Kupffer cells. In contrast, the protective effect of allopurinol treatment suggests that, similar to the mechanism in parenchymal cells, mitochondrial oxidant stress and peroxynitrite formation in sinusoidal endothelial cells may be critical for vascular injury after acetaminophen overdose.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.comparative-hepatology.com/content/3/S1/S46en
dc.rights©  Knight and Jaeschke; licensee BioMed Central Ltd 2004en
dc.titlePeroxynitrite formation and sinusoidal endothelial cell injury during acetaminophen-induced hepatotoxicity in miceen
dc.typeArticleen
dc.identifier.eissn1476-5926en
dc.contributor.departmentDepartment of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USAen
dc.contributor.departmentLiver Research Institute, University of Arizona College of Medicine, Room 6309, 1501 N. Campbell Avenue, Arizona 85724, USAen
dc.identifier.journalComparative Hepatologyen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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