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Research Article Free access | 10.1172/JCI115722

Zidovudine induces molecular, biochemical, and ultrastructural changes in rat skeletal muscle mitochondria.

W Lewis, B Gonzalez, A Chomyn, and T Papoian

Department of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine.

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Department of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine.

Find articles by Gonzalez, B. in: PubMed | Google Scholar

Department of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine.

Find articles by Chomyn, A. in: PubMed | Google Scholar

Department of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine.

Find articles by Papoian, T. in: PubMed | Google Scholar

Published April 1, 1992 - More info

Published in Volume 89, Issue 4 on April 1, 1992
J Clin Invest. 1992;89(4):1354–1360. https://doi.org/10.1172/JCI115722.
© 1992 The American Society for Clinical Investigation
Published April 1, 1992 - Version history
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Abstract

Zidovudine (AZT) inhibits HIV-1 replication in AIDS. A limiting side effect is AZT-induced toxic myopathy. Molecular changes in a rat model of AZT-induced toxic myopathy in vivo helped define pathogenetic molecular, biochemical, and ultrastructural toxic events in skeletal muscle and supported clinical and in vitro findings. After 35 d of AZT treatment, selective changes in rat striated muscle were localized ultrastructurally to mitochondria, and included swelling, cristae disruption, and myelin figures. Decreased muscle mitochondrial (mt) DNA, mtRNA, and decreased mitochondrial polypeptide synthesis in vitro were found in parallel. Mitochondrial molecular changes occurred in absence of altered abundance of cytosolic glyceraldehyde-3-phosphate dehydrogenase, or sarcomeric mitochondrial creatine kinase mRNAs. Quadriceps mitochondrial DNA polymerase gamma activity was similar in both AZT-treated and control rats. In vivo findings with rats support the hypothesis that AZT-induced inhibition of mtDNA replication has an effect of depressing the abundance of striated muscle mtDNA, mtRNA, and mitochondrial polypeptide synthesis. This experimental approach may be useful to examine mitochondrial or toxic myopathies.

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