d-methionine (d-met) significantly rescues noise-induced hearing loss: Timing studies

We have previously reported rescue from noise-induced auditory brainstem response (ABR) threshold shifts with d-methionine (d-met) administration 1 h after noise exposure. The present study investigated further d-met rescue intervals at 3, 5 and 7 h post-noise exposure. Chinchillas laniger were exposed to a 6 h 105 dB sound pressure level (dB SPL) octave band noise (OBN) and then administered d-met i.p. starting 3, 5, or 7 h after noise exposure; controls received saline i.p. immediately after noise exposure. ABR assessments were performed at baseline and on post-exposure days 1 and 21. Outer hair cell (OHC) loss was measured in cochleae obtained at sacrifice 21 days post-exposure. Administration of d-met starting at any of the delay times of 3–7 h post-noise exposure significantly reduced day 21 ABR threshold shift at 2 and 4 kHz and OHC loss at all hair cell regions measured (2, 4, 6 and 8 kHz). ABR threshold shifts in the control group at 6 and 8 kHz were only 8 and 11 dB respectively allowing little opportunity to observe protection at those 2 frequencies.

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► D-met provides consistent, significant rescue from noise-induced hearing loss (PTS).
► Rescue is significant even if D-met is delayed up to 7 hours after noise exposure.
► D-met rescue includes protection from ABR threshold shift and outer hair cell loss.
► Rescue from permanent, but not temporary, threshold shift is consistent in studies.
► We predict protection may be seen with epochs beyond 7 hours.