An experimental study of ototoxicity induced by deferoxamine mesilate

Abstract

We investigate the possibility of ototoxicity induced by deferoxamine mesilate (DFO). DFO was administered to guinea pigs intraperitoneally at 200 or 400mg/kg body weight/day, 6 days/week for 5 weeks, or 600mg/kg body weight/day, 6 days/week for 4 weeks. Physiological saline instead of DFO was given to animals as a control. After the course of administration was completed, we measured the threshold of the compound action potential (CAP) and the endocochlear potential (EP). We also examined the cochlear histology by scanning electron microscopy. The CAP threshold of animals treated with 200 or 400mg of DFO per kg was not elevated. In the animals treated with 600mg/kg, however, the CAP threshold was clearly elevated when compared with that of control animals. The EP values of animals treated with 200 or 400mg of DFO per kg were comparable to those of control animals. In some animals treated with 600mg of DFO per kg, however, the EP values were decreased. Histological examination revealed that the outer hair cells of the cochlea were missing. DFO presumably acts on hair cells, resulting in elevation of the CAP threshold. We concluded that hair cell damage is one of the contributing factors to CAP threshold elevation.