Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells
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Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells

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Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells

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dc.contributor.author Apostolova, Nadezda es_ES
dc.contributor.author Gómez Sucerquia, Leysa Jackeline es_ES
dc.contributor.author Moran, A es_ES
dc.contributor.author Alvarez, A es_ES
dc.contributor.author Blas García, Ana es_ES
dc.contributor.author Esplugues Mota, Juan Vicente es_ES
dc.date.accessioned 2015-06-29T10:34:11Z
dc.date.available 2015-06-29T10:34:11Z
dc.date.issued 2010 es_ES
dc.identifier.uri http://hdl.handle.net/10550/44813
dc.description.abstract BACKGROUND AND PURPOSEEfavirenz (EFV) is widely used in the treatment of HIV-1 infection. Though highly efficient, there is growing concern about EFV-related side effects, the molecular basis of which remains elusive.EXPERIMENTAL APPROACHIn vitro studies were performed to address the effect of clinically relevant concentrations of EFV (10, 25 and 50 µM) on human hepatic cells.KEY RESULTSCellular proliferation and viability were reduced in a concentration-dependent manner. Analyses of the cell cycle and several cell death parameters (chromatin condensation, phosphatidylserine exteriorization, mitochondrial proapoptotic protein translocation and caspase activation) revealed that EFV triggered apoptosis via the intrinsic pathway. In addition, EFV directly affected mitochondrial function in a reversible manner, inducing a decrease in mitochondrial membrane potential and an increase in mitochondrial superoxide production, followed by a reduction in cellular glutathione content. The rapidity of these actions rules out any involvement of mitochondrial DNA replication, which, until now, was thought to be the main mechanism of mitochondrial toxicity of antiretroviral drugs. Importantly, we also observed an increase in mitochondrial mass, manifested as an elevated cardiolipin content and enhanced expression of mitochondrial proteins, which was not paralleled by an increase in the mtDNA/nuclear DNA copy number ratio. The toxic effect of EFV was partially reversed by antioxidant pretreatment, which suggests ROS generation is involved in this effect.CONCLUSION AND IMPLICATIONSClinically relevant concentrations of EFV were shown to be mitotoxic in human hepatic cells in vitro, which may be pertinent to the understanding of the hepatotoxicity associated with this drug. es_ES
dc.source British Journal of Pharmacology Vol. 160 Issue 8: pp. 2069-2084 es_ES
dc.subject reactive oxygen species es_ES
dc.subject antiretroviral drugs es_ES
dc.subject hepatotoxicity es_ES
dc.subject cell death es_ES
dc.subject side effects es_ES
dc.subject Efavirenz es_ES
dc.subject mitochondria es_ES
dc.title Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.identifier.doi 10.1111/j.1476-5381.2010.00866.x es_ES
dc.identifier.idgrec 073684 es_ES

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