Zidovudine (AZT) causes an oxidation of mitochondrial DNA in mouse liver. NLM AIDSLINE Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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Zidovudine (AZT) causes an oxidation of mitochondrial DNA in mouse liver.

Hepatology. 1999 Mar;29(3):985-7. Unique Identifier : AIDSLINE MED/99162396
de la Asuncion JG; del Olmo ML; Sastre J; Pallardo FV; Vina J; Departamento de Fisiologia, Facultad de Medicina, Universidad de; Valencia, Valencia, Spain.

Abstract: Zidovudine (3'-azido-2',3'-dideoxythymidine [AZT]) inhibits human immunodeficiency virus replication and delays progression of acquired immune deficiency syndrome. We have recently found that, in muscle, AZT causes oxidative damage to mitochondrial DNA (mtDNA) and other signs of mitochondrial oxidative damage. The aim of this work was to test if AZT causes oxidative damage to liver mtDNA. In our study, an experimental mouse model was used in which mice were administered AZT (10 mg/kg body weight/d) in drinking water. Liver mtDNA of mice treated with AZT had 40% more of the oxidized, mutagenic nucleoside, 8-oxo-7,8-dihydroxy-2'deoxyguanosine (8-oxo-dG) than untreated controls. This oxidative damage to mtDNA is caused by a significant increase (of over 240%) in peroxide production by liver mitochondria from AZT-treated mice, which was prevented by dietary administration with vitamins C and E.
Keywords: JOURNAL ARTICLE Animal Anti-HIV Agents/*PHARMACOLOGY Deoxyguanosine/ANALOGS & DERIVATIVES/METABOLISM DNA, Mitochondrial/*DRUG EFFECTS/*METABOLISM Liver/*METABOLISM Male Mice Mice, Inbred Strains Mitochondria, Liver/METABOLISM Oxidation-Reduction Peroxides/METABOLISM Support, Non-U.S. Gov't Zidovudine/*PHARMACOLOGYKWDjournalarticleanimalanti-hivagents/KWDpharmacologydeoxyguanosine/analogs&derivatives/metabolismdna,mitochondrial/KWDdrugeffects/KWDmetabolismliver/KWDmetabolismmalemicemice,inbredstrainsmitochondria,liver/metabolismoxidation-reductionperoxides/metabolismsupport,non-uKWDsKWDgov'tzidovudine/KWDpharmacology
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