AZT oxidative damage in the liver

Abstract (1) Zidovudine or AZT was the first antiretroviral drug approved by FDA in 1987 and is the most common drug administered to HIV-infected patients with high efficacy in controlling the retrovirus proliferation but with important secondary toxic effects on the muscular and the hepatic tissue. (2) This azo-deoxythymidine analog may induce genetic alterations of the nuclear DNA with the concomitant consequences, but also AZT may induce damage of the mitochondrial DNA that may result in the biosynthesis of abnormal respiratory complexes that impaired oxidative energy production. (3) The mitochondrial toxicity of AZT also can be attributed to its direct inhibition of the oxidative energy generation, particularly of the respiratory complex I, leading to the production of reactive oxygen species. (4) In liver tissue, the ROS induced by AZT administration is involved in fat accumulation (liver steatosis) and inflammation. (5) Since AZT administration also induces an apparent “antioxidant” inhibition of cell proliferation, it results difficult to conciliate that the main mechanism underlying AZT liver toxicity rests solely in the generation of oxidant/nitrosative stress.