Abstract
Previous studies have shown that the antiviral nucleoside analogue zidovudine (AZT) depletes levels of mitochondrial DNA (mtDNA) in muscle of patients on long-term therapy. In this study we found that in a similar group of eight HIV-positive patients receiving AZT there was no depletion of brain mtDNA. This finding suggests that AZT related mtDNA depletion is not a contributing factor in the HIV encephalopathy that occurs in a proportion of HIV positive patients receiving this antiviral agent.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
An S-F, Ciardi A, Scaravilli F (1994) PCR detection of HIV proviral DNA in the brains of AIDS patients: comparison between results using fresh frozen and paraffin embedded specimens. J Clin Pathol 47:990–994
Arnaudo E, Dalakas M, Shanske S, Moraes CT, DiMauro S, Schon EA (1991) Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy. Lancet 337:508–510
Bebenek K, Thomas DC, Roberts JD, Eckstein F, Kunkel TA (1993) Effects of AZT metabolites on simian virus 40 origin-dependent replication and heteroduplex repair in HeLa cell extracts. Mol Pharmacol 43:57–63
Chalmers AC, Greco CM, Miller RG (1991) Progress in AZT myopathy. Neurology 41:1181–1184
Dalakas MC, Illa I, Pezeshkpour GH, Lankaitis JP, Cohen BC, Griffin JL (1990) Long term therapy with AZT can cause mitochondrial myopathy indistinguishable from myopathy associated with HIV. N Engl J Med 322:1098–1105
Eymard B, Hauw J-J (1992) Mitochondrial encephalopathies. Curr Opim Neurol Neurosurg 5:909–916
Gillespie D, Habbell HR, Carter WA, et al (1994) Synergistic inhibition of AZT-resistant HIV by AZT combined with poly(I):poly(C12U) without synergistic toxicity to bone marrow progenitor cell elements In Vivo 8:375–381
Gray F, Geny C, Dournon E, Fenelon G, Lionnet F, Gherardi R (1991) Neuropathological evidence that zidovudine reduces incidence of HIV infection of brain. Lancet 337:852–853
Gross NJ, Getz GS, Rabinowitz M (1969) Apparent turnover of mitochondrial DNA and phospholipids in the tissues of the rat. J Biol Chem 244:1552–1556
Hayakawa M, Ogawa T, Sugiyama S, Tanaka M, Ozawa T (1991) Massive conversion of guanosine to 8-hydroxyguanosine in mouse liver mitochondrial DNA by administration of AZT. Biochem Biophys Res Commun 176: 87–93
Lewis W, Dalakas MC (1993) Mitochondrial cytotoxicity of antiviral drugs. Nature Med 1:417–422
Sato M, Murao K, Mizobuchi M, Takahara J (1993) Quantitative and sensitive northern blot hybridisation using PCR-generated DNA probes labelled with digoxigenin by nick translation. Biotechniques 15:880–882
Sidtis JL, Gatsonis G, Price RW, et al (1993) Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled trial. Ann Neurol 33:343–349
Simpson MV, Chin CD, Keilbaugh SA, Lin T-S, Prusoff WH (1989) Studies on the inhibition of mitochondrial DNA replication by 3′-azido-3′-deoxythymidine and other dideoxynucleoside analogues which inhibit HIV-1 replication. Biochem Pharmacol 38:1033–1036
Swartz MN (1995) Mitochondrial toxicity - new adverse drug affects. N Engl J Med 333:1146–1148
Tritschler HJ, Andretta F, Moraes CT, et al (1992) Mitochondrial myopathy of childhood associated with depletion of mitochondrial DNA. Neurology 42: 209–217
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Davison, F.D., Sweeney, B.J. & Scaravilli, F. Mitochondrial DNA levels in the brain of HIV-positive patients after zidovudine therapy. J Neurol 243, 648–651 (1996). https://doi.org/10.1007/BF00878661
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00878661