Dose-dependent changes in the rat cochlea following aminoglycoside intoxication. II. Histological study.
The structural damages induced by a range of amikacin doses have been studied with SEM and TEM in the adult rat cochlea. Six groups of rats were given daily subcutaneous amikacin injections of either 200, 400, 600, 700, 800, or 1000 mg/kg per day for five consecutive days. Observations were made one month after the end of treatment, following functional recordings [(1987) Hear. Res. 26, 191-197]. In the group treated with 200 mg/kg per day, neither SEM nor TEM revealed any cochlear abnormalities. In the 400-mg group, the only damages were cytoplasmic abnormalities in the OHCs. Changes in the OHC stereocilia occurred at higher doses and were always associated with severe alterations of the underlying cell body. The first missing hair cells were OHCs in the apical regions of the cochleas of the 600-mg group. In the 700-mg group, the loss of OHCs extended to the middle and basal regions, mainly in the third row. By contrast, in the 800- and 1000-mg groups, the usual pattern of hair-cell degeneration was found. Loss of hair cells was greatest in the basal cochlear regions, where the first row of OHCs was more extensively destroyed. These results indicate that metabolic disorders (only visible with TEM) precede stereociliary alterations. Under SEM, the pattern of hair cell degeneration appeared to depend on the dose of the drug. The study clearly demonstrates that both SEM and TEM are needed to determine the true condition of hair cells after drug intoxication.
D000583:Amikacin / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002923:Cilia / Q000187:drug effects / Q000648:ultrastructure; D003051:Cochlea / Q000187:drug effects* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000648:ultrastructure; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D051381:Rats
D000583:Amikacin