Detection of tobramycin- and netilmicin-induced ototoxicity in guinea pigs with evoked action potentials.
To evaluate the action potentials evoked in the cochlea in aminoglycoside-induced ototoxicity, 80 guinea pigs were given 25, 50, 75, or 100 mg of tobramycin or netilmicin/kg per day for 14 or 28 days. Ten other guinea pigs (controls) were given 200 mg of ampicillin/kg per day for 14 or 28 days. Cochlear evoked action potentials (CEAP) before and after treatment were measured, and the cochlea was examined microscopically after treatment. Comparison of initial and final values showed that the threshold of the main negative (N1) wave rose (p less than 0.00001 for dose and duration factors), the amplitude decreased (P less than 0.00001 for dose factors at sound intensities of 120 and 90 dB, P less than 0.001 at 70 dB), and the latency lengthened (P less than 0.0001 for dose factors at 120 and 90 dB). The CEAP method appeared to be more sensitive than microscopic examination of the cochlea for detection of ototoxicity induced by the lower dosages of the aminoglycosides. No significant differences were observed between the effects of tobramycin and netilmicin. In conclusion, the CEAP method appears to be a promising tool for detection of aminoglycoside-induced ototoxicity.
D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects; D000667:Ampicillin / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005839:Gentamicins / Q000633:toxicity*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D009428:Netilmicin / Q000633:toxicity*; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors; D014031:Tobramycin / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009428:Netilmicin; D000667:Ampicillin; D014031:Tobramycin