モルモットにおけるAminodeoxykanamycinの耳毒性に関する実験的研究

耳介反射および病理組織学的所見

抄録

The present study has been performed to reevaluate the ototoxicity of aminodeoxykanamycin (AKM) and to compare its ototoxicity with that of kanamycid (KM).
Material and method:
Fifty male albi n o guinea pigs (300 g body weight at the start of the experiment) of the Hartley strain were divided into 5 groups. AKM was given to the guinea pigs intramuscularly for 28 days i n the following different dose: 40 mg/kg, 80 mg/kg and 200 mg/kg. On the other hand, KM war a dministered intramuscularly to the guinea pigs for 28 days at the 2 different dose: 200 mg/kg and 4 00 mg/kg, respectively. The each group consisted of 10 guinea pigs. The pinna reflex test of the experimental animals was carried out with the audiometer for the guinea pig before, during and after t he injection of the antibiotics. After the intravital perfusion of the Wittmaack's fixative through the aorta of the animals the bilateral ears were removed, fixed, decalcified and embedded in celloid i n. The horizontal serial sections of the ears were stained with hematoxylin-eosin and examined histopathologically.
Results:
1. No evidence of ototoxicity was noted histopathologically in the guinea pigs received intramuscularly AKM 40 mg/kg body weight for 28 days (1, 120 mg of total dose) and AKM 80 mg/ kg for 28 days (2, 240 mg of total dose), respectively.
2. Ototoxicity was found in 40% of the 10 guinea pigs received intramuscularly AKM 200 mg/kg for 28 days (5, 600 mg of total dose). These animals with ototoxicity showed the loss of pinna reflex in the region over 8, 000 cps and histopathologically the disappearance of the outer hair cells o f the organ of Corti in the lower turn of the cochlea. The damage of the vestibular organ was not observe d.
3. The incidence in the loss of the outer hair cells of the organ of Corti was 40% in the gu i nea pigs (10) received intramuscularly AKM 200 mg/kg body weight for 28 days.
4. Histopathologically, the ototoxicity of the guinea pig group rece i ved intramuscularly AKM 200 mg/kg body weight for 28 days seems to be similar to that of the group received intramuscularly KM 400 mg/kg for 28 days.
5. The guinea p i g s (AKM 200 mg/kg for 28 days) with severe otoxicity showed histopathologically relatively pronounced interstitial nephritis.