Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.freeradbiomed.2005.05.013
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dc.titleMitochondrial permeability transition as a source of superoxide anion induced by the nitroaromatic drug nimesulide in vitro
dc.contributor.authorTay, V.K.S.
dc.contributor.authorWang, A.S.
dc.contributor.authorLeow, K.Y.
dc.contributor.authorOng, M.M.K.
dc.contributor.authorBoelsterli, U.A.
dc.contributor.authorWong, K.P.
dc.date.accessioned2011-09-29T05:54:57Z
dc.date.available2011-09-29T05:54:57Z
dc.date.issued2005
dc.identifier.citationTay, V.K.S., Wang, A.S., Leow, K.Y., Ong, M.M.K., Boelsterli, U.A., Wong, K.P. (2005). Mitochondrial permeability transition as a source of superoxide anion induced by the nitroaromatic drug nimesulide in vitro. Free Radical Biology and Medicine 39 (7) : 949-959. ScholarBank@NUS Repository. https://doi.org/10.1016/j.freeradbiomed.2005.05.013
dc.identifier.issn08915849
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/27309
dc.description.abstractNimesulide, a widely used nonsteroidal anti-inflammatory drag containing a nitroaromatic moiety, has been associated with rare but serious hepatic adverse effects. The mechanisms underlying this idiosyncratic hepatotoxicity are unknown; however, both mitochondrial injury and oxidative stress have been implicated in contributing to liver injury in susceptible patients. The aim of this study was, first, to explore whether membrane permeability transition (MPT) could contribute to nimesulide's mitochondrial toxicity and, second, whether metabolism-derived reactive oxygen species (ROS) were responsible for MPT. We found that isolated mouse liver mitochondria readily underwent Ca 2+-dependent, cyclosporin A-sensitive MPT upon exposure to nimesulide (at ≥ 3 μM). Net increases in mitochondrial superoxide anion levels, determined with the fluorescent probe dihydroethidium, were induced by nimesulide only in the presence of Ca2+ and were cyclosporin A-sensitive, indicating that superoxide production was a consequence, rather than the cause, of MPT. In addition, nimesulide caused a rapid dissipation of the inner mitochondrial transmembrane potential (at ≥ 3 μM), followed by a concentration-dependent decrease in ATP biosynthesis. Because nimesulide, unlike the related nitroaromatic drag nilutamide, did not produce any detectable ROS during incubation with mouse hepatic microsomes, we conclude that mitochondrial uncoupling causes MPT and that ROS production is a secondary effect. © 2005 Elsevier Inc. All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.freeradbiomed.2005.05.013
dc.sourceScopus
dc.subjectFree radicals
dc.subjectMembrane permeability transition
dc.subjectMitochondria
dc.subjectNimesulide
dc.subjectNitroaromatic drug
dc.subjectSuperoxide anion
dc.subjectUncoupling
dc.typeArticle
dc.contributor.departmentPHARMACOLOGY
dc.description.doi10.1016/j.freeradbiomed.2005.05.013
dc.description.sourcetitleFree Radical Biology and Medicine
dc.description.volume39
dc.description.issue7
dc.description.page949-959
dc.identifier.isiut000231931600010
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