ABSTRACT
AIDS patients who receive zidovudine (AZT) frequently suffer from myopathy (1). The typical features of this myopathy are ragged red fibers and paracrystalline inclusions in mitochondria. This has been attributed to damage to mitochondria, and specifically to mitochondrial DNA (2). In 1991 it was proposed that AZT causes oxidation of guanosine to 8-hydroxy-2'-deoxyguanosine in experimental animals (3). The role of mitochondrial DNA in cell physiology and medicine has been emphasized (4). We have developed a new method to determine accurately glutathione redox status in blood (5,6). Using this method, we have recently observed that there is a correlation between glutathione oxidation and damage to mitochondrial DNA both in rats and in mice and that damage to mitochondrial DNA can be prevented by administration of antioxidants (7). The aims of the present work were to test whether AIDS causes oxidation of blood glutathione and to determine whether the mitochondrial damage caused by AZT, both in humans and in experimental animals, is due to damage to mitochondrial DNA.
