Aminoglycosides activate oxygen metabolites production in the cochlea of mature and developing rats

The ototoxicity of antibiotics, particularly of aminoglycosides, is a well-known undesirable side effect which may be based on a free radical mechanism. We studied the effect of different antibiotics in the production of reactive oxygen species in freshly isolated cochleas of mature and 2-10 weeks old developing rats. Phorbol myristate acetate induced the release of reactive oxygen species after a lag time close to 30 s and declined back to basal values in 10-20 min. The rate of reactive oxygen species production correlated inversely to the age in 2-10 weeks old rats. The study of a set of antibiotics showed that a very low concentration of gentamicin and streptomycin (10-100 ng/ml) enhanced the effect of phorbol myristate acetate. At the above-indicated concentrations, ciprofloxacin did not modify phorbol myristate acetate-induced activation. These results show the enhancement by aminoglycosides of reactive oxygen species production in cochlear tissues, particularly in developing rats.