Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.taap.2006.12.013
DC FieldValue
dc.titleMitochondrial abnormalities-A link to idiosyncratic drug hepatotoxicity?
dc.contributor.authorBoelsterli, U.A.
dc.contributor.authorLim, P.L.K.
dc.date.accessioned2011-09-29T05:55:19Z
dc.date.available2011-09-29T05:55:19Z
dc.date.issued2007
dc.identifier.citationBoelsterli, U.A., Lim, P.L.K. (2007). Mitochondrial abnormalities-A link to idiosyncratic drug hepatotoxicity?. Toxicology and Applied Pharmacology 220 (1) : 92-107. ScholarBank@NUS Repository. https://doi.org/10.1016/j.taap.2006.12.013
dc.identifier.issn0041008X
dc.identifier.issn10960333
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/27343
dc.description.abstractIdiosyncratic drug-induced liver injury (DILI) is a major clinical problem and poses a considerable challenge for drug development as an increasing number of successfully launched drugs or new potential drugs have been implicated in causing DILI in susceptible patient subsets. Although the incidence for a particular drug is very low (yet grossly underestimated), the outcome of DILI can be serious. Unfortunately, prediction has remained poor (both for patients at risk and for new chemical entities). The underlying mechanisms and the determinants of susceptibility have largely remained ill-defined. The aim of this review is to provide both clinical and experimental evidence for a major role of mitochondria both as a target of drugs causing idiosyncratic DILI and as mediators of delayed liver injury. We develop a unifying hypothesis that involves underlying genetic or acquired mitochondrial abnormalities as a major determinant of susceptibility for a number of drugs that target mitochondria and cause DILI. The mitochondrial hypothesis, implying gradually accumulating and initially silent mitochondrial injury in heteroplasmic cells which reaches a critical threshold and abruptly triggers liver injury, is consistent with the findings that typically idiosyncratic DILI is delayed (by weeks or months), that increasing age and female gender are risk factors and that these drugs are targeted to the liver and clearly exhibit a mitochondrial hazard in vitro and in vivo. New animal models (e.g., the Sod2+/- mouse) provide supporting evidence for this concept. However, genetic analyses of DILI patient samples are needed to ultimately provide the proof-of-concept. © 2006 Elsevier Inc. All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.taap.2006.12.013
dc.sourceScopus
dc.subjectDrug idiosyncrasy
dc.subjectDrug-induced liver injury
dc.subjectMitochondria
dc.subjectOxidative stress
dc.subjectSusceptibility factors
dc.typeReview
dc.contributor.departmentPHARMACOLOGY
dc.description.doi10.1016/j.taap.2006.12.013
dc.description.sourcetitleToxicology and Applied Pharmacology
dc.description.volume220
dc.description.issue1
dc.description.page92-107
dc.identifier.isiut000245325600010
Appears in Collections:Staff Publications

Show simple item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

178
checked on Oct 3, 2022

WEB OF SCIENCETM
Citations

164
checked on Oct 3, 2022

Page view(s)

255
checked on Sep 22, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.