Protection against noise-induced hearing loss in young CBA/J mice by low-dose kanamycin.
Animal studies indicate that a combination of kanamycin (KM) and noise produces a synergistic effect, whereby the threshold shift from the combination is greater than the sum of the shifts caused by either agent alone. Most such studies have focused on adult animals, and it has remained unclear whether younger, presumably more susceptible, animals show an even greater synergistic effect. The present study tested the hypothesis that young CBA/J mice receiving a low dose of KM (300 mg/kg, 2x/day, s.c.) from 20 to 30 days post-gestational age followed by brief noise exposure (110 dB SPL; 4-45 kHz, 30 s) would show greater noise-induced permanent threshold shifts (NIPTS) than mice receiving either treatment alone. Noise exposure produced 30-40 dB of NIPTS and moderate hair cell loss in young saline-treated mice. KM alone at this dose had no effect on thresholds. Surprisingly, mice receiving KM plus noise were protected from NIPTS, showing ABR thresholds not significantly different from unexposed controls. Mice receiving KM prior to noise exposure also showed significantly less outer hair cell loss than saline-treated mice. Additional experiments indicated protection by KM when the noise was applied either 24 or 48 h after the last KM injection. Our results demonstrate a powerful protective effect of sub-chronic low-dose kanamycin against NIPTS in young CBA/J mice. Repeated kanamycin exposure may establish a preconditioned protective state, the molecular bases of which remain to be determined.
Fernandez
Elizabeth A
EA
Program in Audiology and Communication Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ohlemiller
Kevin K
KK
Gagnon
Patricia M
PM
Clark
William W
WW
D000222:Adaptation, Physiological / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000473:pathology / Q000517:prevention & control*; D007612:Kanamycin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009622:Noise / Q000009:adverse effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D011500:Protein Synthesis Inhibitors; D007612:Kanamycin