Microsomal oxidative damage promoted by acetaminophen metabolism
Author
dc.contributor.author
Letelier Muñoz, María Eugenia
Author
dc.contributor.author
López Valladares, Miguel
es_CL
Author
dc.contributor.author
Peredo Silva, Liliana
es_CL
Author
dc.contributor.author
Rojas Sepúlveda, Daniel
es_CL
Author
dc.contributor.author
Aracena, Paula
es_CL
Admission date
dc.date.accessioned
2014-01-07T19:22:55Z
Available date
dc.date.available
2014-01-07T19:22:55Z
Publication date
dc.date.issued
2011-10
Cita de ítem
dc.identifier.citation
TOXICOLOGY IN VITRO Volume: 25 Issue: 7 Pages: 1310-1313 Published: OCT 2011
en_US
Identifier
dc.identifier.other
DOI: 10.1016/j.tiv.2011.04.022
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/121705
General note
dc.description
Artículo de publicación ISI
en_US
Abstract
dc.description.abstract
Adverse reactions of acetaminophen have been associated to oxidative stress, which may be elicited by
reactive oxygen species (ROS) and/or production of the metabolite NAPQI. Both phenomena would arise
through the activity of liver cytochrome P450 (CYP450) system, but their contribution to this oxidative
stress is yet to be clarified. A NADPH oxidase activity has been proposed in rat liver microsomes. This
activity may be due to the presence of NAD(P)H oxidase (NOX) isoforms in liver endoplasmic reticulum.
Both NOX and the CYP450 system activities can catalyze ROS generation using NADPH as a cofactor.
Therefore, acetaminophen biotransformation, which requires NADPH, may promote ROS generation
through either activity or both. To discriminate between these possibilities, rat liver microsomes were
incubated with acetaminophen and NADPH in the presence or absence of specific inhibitors. Incubation
with NADPH and acetaminophen elicited lipid peroxidation and decreased thiol content and glutathione-
S-transferase (GST) activity. The NOX inhibitors apocynin and plumbagin prevented all these phenomena
but the decrease in thiol content. In contrast, this decrease was completely prevented by the specific
CYP450 system inhibitor SKF-525A. These data suggest that ROS generation following incubation of
microsomes with acetaminophen and NADPH appears to be mainly caused by a NOX activity. In light
of these data, toxicity of acetaminophen is discussed.