Effects of short-term zidovudine exposure on mitochondrial DNA content and succinate dehydrogenase activity of rat skeletal muscle cells

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dc.contributor.authorKiyomoto, Beatriz H. [UNIFESP]
dc.contributor.authorTengan, Celia H. [UNIFESP]
dc.contributor.authorGodinho, Rosely O. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:51:23Z
dc.date.available2016-01-24T13:51:23Z
dc.date.issued2008-05-15
dc.description.abstractLong-term use of zidovudine (AZT) may cause mitochondrial abnormalities in various tissues, including a toxic myopathy in AIDS patients associated with mitochondrial DNA (mtDNA) depletion. in the present study, we examine the short-term (48 h) effect of AZT (10, 30 and 100 mu g/ml) on the mitochondrial succinate dehydrogenase (SDH) and mtDNA content of rat cultured skeletal muscle. the effect of AZT on cytochrome c oxidase (COX) enzyme was also analyzed. the histochemical quantitative analysis of SDH showed that AZT 10, 30 and 100 mu g/ml increased by 7%, 9% and 13% the mitochondrial content. Conversely, treatment of rat cultures with 10 to 100 mu g/ml AZT reduced the mtDNA content by 23% to 66%, when compared to control values. the spontaneous contraction and the COX activity were not modified by up to 100 mu g/ml AZT. Taken together, these results show that short-term treatment with AZT can induce severe myotoxicity that involves mitochondrial proliferation and mtDNA depletion in the rat cultured myotubes. Our results also indicate that rat cultured skeletal muscle might be a valuable in vitro assay to evaluate the effect of drugs on mitochondria to predict their potential to induce mitochondrial toxicity. (C) 2007 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol INFAR, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Neurol & Neurosurg, BR-04039032 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol INFAR, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Neurol & Neurosurg, BR-04039032 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent33-39
dc.identifierhttp://dx.doi.org/10.1016/j.jns.2007.10.026
dc.identifier.citationJournal of the Neurological Sciences. Amsterdam: Elsevier B.V., v. 268, n. 1-2, p. 33-39, 2008.
dc.identifier.doi10.1016/j.jns.2007.10.026
dc.identifier.issn0022-510X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/30666
dc.identifier.wosWOS:000255261800006
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofJournal of the Neurological Sciences
dc.rightsAcesso restrito
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectzidovudineen
dc.subjectskeletal muscleen
dc.subjectmitochondriaen
dc.subjectsuccinate dehydrogenaseen
dc.subjectmitochondrial DNAen
dc.titleEffects of short-term zidovudine exposure on mitochondrial DNA content and succinate dehydrogenase activity of rat skeletal muscle cellsen
dc.typeArtigo
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