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

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

Author Kiyomoto, Beatriz H. Autor UNIFESP Google Scholar
Tengan, Celia H. Autor UNIFESP Google Scholar
Godinho, Rosely O. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Long-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.
Keywords zidovudine
skeletal muscle
mitochondria
succinate dehydrogenase
mitochondrial DNA
Language English
Date 2008-05-15
Published in Journal of the Neurological Sciences. Amsterdam: Elsevier B.V., v. 268, n. 1-2, p. 33-39, 2008.
ISSN 0022-510X (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 33-39
Origin http://dx.doi.org/10.1016/j.jns.2007.10.026
Access rights Closed access
Type Article
Web of Science ID WOS:000255261800006
URI http://repositorio.unifesp.br/handle/11600/30666

Show full item record




File

File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account