Comparative surface studies of ototoxic effects of various aminoglycoside antibiotics on the organ of Corti in the guinea pig. A scanning electron microscopic study

Abstract

It was the purpose of this study to establish criteria for use in comparing the toxic effects of aminoglycosid antibiotics on the organ of Corti by means of scanning electron microscopy. Amikacin, Tobramycin and Gentamicin were administered twice a day subcutaneously for 10 days to healthy guinea pigs. One group of animals was sacrificed 1 day after completion of the treatment; the other group was allowed to survive 22 days. Depending upon the dosage of the administered drug, Amikacin (150 mg per kg body weight daily, corresponding to 10 times an average recommended human dose) caused pronounced outer hair cell damage even 1 day after the treatment was stopped. At this time Gentamicin and Tobramycin (150 mg per kg body weight daily, corresponding to 50 times an average human dose) showed less damage. After 22 days' survival, late toxic effects were found mainly in Gentamicin- and Tobramycin-treated animals. After 3 weeks, nearly total outer hair cell loss was found in the basal coil, while the 2nd and 3rd coils were often less severely damaged. At this time Amikacin-treated animals showed severe damage in all coils. 300 mg per kg body weight Amikacin (i.e. 20 times the average human dose) showed about the same toxic effect on sensory cells of the guinea pig as did 150 mg Gentamicin or Tobramycin per kg body weight. We are conscious of the fact that there are problems in correlating the weight of a drug and its probable toxic effect. In comparative animal experiments we consider it useful to standardize the time of exposure, the amount of drug administered (e.g. related to the human dose) and the survival time.