Ototoxicity of tobramycin in young adult and old rats.
To study the possible age-dependent ototoxic effects of tobramycin a subacute toxicity study was performed. To young adult (3 months) and old (27-30 months) female Wag-Rij rats 0, 10, 40, and 160 mg tobramycin sulfate/kg was administered subcutaneously in two doses a day. After 14 days all animals were autopsied. The cochlea was fixed by perfusion through the opened oval window and prepared for scanning electron microscopy. The rat cochlea consists of two turns. In all animals of the young control group the row of inner hair cells (IHC) as well as the three rows of outer hair cells (OHC) of the organ of Corti were fully intact. IHC as well as OHC are provided with three rows of stereocilia, from inside to outside with increasing length. The stereocilia of OHC are arranged in a characteristic W-configuration. In the young low dose group effects were focally seen in only 1 of 10 rats, consisting of shortened, disoriented or partly disappeared stereocilia of IHC and OHC in the basal turn. In the young mid dose group 4 of 10 animals had focally shortened, disoriented, and less stereocilia in the first row of OHC in the basal turn, and once of IHC and OHC in the apical turn. Seven of 8 animals of the young high dose group showed effects consisting of focal loss or shortening of stereocilia of IHC and OHC of the apical turn (3x), of OHC in the basal turn (3x), and once of stereocilia of IHC only. In the old control group the stereocilia of IHC were fully intact. However, many OHC, independent of row or turn, had no stereocilia at all. The percentages of OHC without stereocilia in the three rows of the apical and basal turns were 44-10-50 and 40-20-50, respectively. In the old low, mid, and high dose group the percentages of OHC without stereocilia were nearly identical to those of the old control group. In the old low and high dose group a reduced number of stereocilia per IHC occurred in half of the number of animals, while in the mid dose group the IHC were fully intact. In young adult animals the number of mildly affected cochleae increased as well as the extent of the lesion increased with increasing dose of tobramycin. The lesions of IHC and OHC, consisting of a decrease in number or shortening of stereocilia, were restricted mainly to (the last part of) the basal turn. As old control rats showed already a large number of OHC without stereocilia, the possible ototoxic effects of tobramycin were not detected against this "background" of stereociliary loss, consistent with aging. The damage in old rats was certainly not greater than in young adult rats. In conclusion, old rats were not more sensitive to the possible ototoxic effects of tobramycin than young adult rats.
Dormans
J A
JA
Laboratory for Pathology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
Peters-Volleberg
G W
GW
Dortant
P M
PM
Speijers
G J
GJ
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005260:Female; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D007279:Injections, Subcutaneous; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D014031:Tobramycin / Q000008:administration & dosage / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D014031:Tobramycin