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

Zidovudine (3'-azido-2',3'-dideoxythymidine [AZT]) inhibits human immunodef iciency virus replication and delays progression of acquired immune deficie ncy syndrome. We have recently found that, in muscle, AZT causes oxidative damage to mitochondrial DNA (mtDNA) and other signs of mitochondrial oxidat ive 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 whic h mice were administered AZT (10 mg/kg body weight/d) in drinking water. Li ver mtDNA of mice treated with AZT had 40% more of the oxidized, mutagenic nucleoside, 8-ore-7,8-dihydroxy-2' deoxyguanosine (8-oxo-dG) than untreated controls. This oxidative damage to mtDNA is caused by a significant increa se (of over 240%) in peroxide production by liver mitochondria from AZT-tre ated mice, which was prevented by dietary administration with vitamins C an d E.