Gc. Marean et al., REGENERATED HAIR-CELLS IN THE EUROPEAN STARLING - ARE THEY MORE RESISTANT TO KANAMYCIN OTOTOXICITY THAN ORIGINAL HAIR-CELLS, Hearing research, 82(2), 1995, pp. 267-276
Previous work from our laboratory [Marean et al. (1993) Hear. Res. 71,
125-136] has shown that a 10 day dose of 200 mg/kg/day kanamycin prod
uced damage to the basal 34% of the starling basilar papilla. We also
observed that repeating the dosing schedule following a 4 month surviv
al period resulted in significantly less damage to the regenerated aud
itory epithelium. The present study investigated whether or not this a
pparent resistance was the result of a tendency for regenerated hair c
ells to be less susceptible to kanamycin ototoxicity, or if other, sys
temic factors may be involved. Eight European starlings were given sub
cutaneous injections of 200 mg/kg/day kanamycin for 10 days. Serum lev
els of kanamycin were measured at the time of sacrifice for all birds,
and the basilar papillae of all birds were examined by scanning elect
ron microscopy (SEM). Two of these birds (Group 1) were sacrificed imm
ediately following the dosing period. Two of the birds were allowed to
survive for 60 days (Group 2). Two of the birds were redosed with 200
mg/kg/day for 10 days after 60 days survival (Group 3). Finally, two
birds were redosed with 250 mg/kg/day until serum levels of kanamycin
were the same as Group 1 when sacrificed(> 9 mu g/ml). The SEM results
showed that the regenerated auditory epthelium of the birds dosed a s
econd time sustained less damage compared to previously untreated ears
, even though the dosing regimen was the same (Group 3 versus Group 1)
. The regenerated auditory epethelium of birds dosed a second time sus
tained the same damage as previously untreated animals when the dosage
was increased to attain similar serum levels (Group 4 versus Group 1)
. These results suggest metabolic changes occur in the starling in res
ponse to the initial dose of kanamycin which do not necessarily involv
e changes in hair cell resistance to ototoxicity.