Ototoxicity of Tuberactinomycin-N in Long-Term Experiment

Abstract

The present experiment was made to evaluate the ototoxicity of tuberactinomycin-N (TUM-N) in long-term administration to the Hartley strain guinea pigs (300g body weight at the start of the experiment) and the ototoxicity was compared with those of capreomycin (CPM) and kanamycin (KM).TUM-N was given to 4 guinea pigs at dosis of 200mg/kg/day intramuscularly for 6 months, and CPM was administered to another 4 at the same dosis for the same period. KM was injected into the remaining 5 at the same dosis intramuscularly for 3 months. Pinna reflex test was performed before, during and after the injection of the antibiotics by audiometer. All of these animals were killed after the end of the experiment and their temporal bones were removed after intravital fixation. Horizontal serial celloidin sections were stained with hematoxylin-eosin and then investigated microscopically.1) Pinna reflex test: The loss of the pinna reflex occurred in the frequency range from 8, 000 to 10, 000Hz in 50% and in the total fraquency range from 250 to 10, 000Hz in the another 50% of the CPM treated animals. The loss of the pinna reflex was detected in the total frequency range in 100% of the KM injected animals. However, there was no animals with the loss or increased threshold of the pinna reflex in the TUM-N treated animals.2) Histopathologically, 50% of the TUM-N treated animals showed the irregular loss of the outer hair cells of the organ of Corti confined to the basal end of the cochlea but the another 50% did not exhibit any remarkable pathologic change of the organ of Corti. In the CPM treated animals, extensive loss of the outer hair cells extending from the basal end to the more upper part than the 2nd turn of cochlea was found in 75%. However, the loss of the outer hair cells was localized in the basal end in the remaining 25%. The KM treated animals showed the more extensive loss of the outer hair cells in 100%.3) These results indicate that TUM-N has the most mild ototoxicity among the antibiotics used in this experiment.