FORMATION OF FREE-RADICALS BY GENTAMICIN AND IRON AND EVIDENCE FOR ANIRON GENTAMICIN COMPLEX

Participation of free radicals in the adverse renal and cochlear side effects of aminoglycoside antibiotics is controversial. We measured th e production of free radicals by gentamicin in vitro through the oxida tion of arachidonic acid. Gentamicin alone (0.05 to 10 mM) did not cau se lipid peroxidation. However, it dramatically promoted radical forma tion in the presence of iron salts. Peroxidation was maximal at 1 mM g entamicin plus 0.1 mM Fe(II)/Fe(III) (0.05 mM FeSO4 and FeCl3 each). A t these iron concentrations, peroxidation was not significant in the a bsence of gentamicin. Since chelators can enhance iron-catalyzed oxida tions, this finding suggested that gentamicin-dependent radical format ion was based upon iron chelation. This hypothesis was tested by measu ring the influence of gentamicin on the oxidation of salicylate by Fe- EDTA complexes, a reaction that is inhibited by competing iron chelato rs. Gentamicin was a concentration-dependent inhibitor. In contrast, c oncentrations of gentamicin as high as 50 mM did not interfere with ir on-independent salicylate oxidation. These results suggest that gentam icin acts as an iron chelator, and that the iron-gentamicin complex is a potent catalyst of free radical formation.