Rescue Treatment with Losartan Induces Sustained Hearing Protection After Acoustic Trauma in Mice

Introduction: Noise trauma impairs cochlear microcirculation, resulting in hearing loss. Losartan, an angiotensin II receptor antagonist, is anti-inflammatory and vasoprotective in diseases of the heart, kidney, and brain and is a promising candidate for attenuating noise-induced hearing loss, with potential long-term effects on protecting hearing levels after noise induction.

Methods: CBA/J mice (age 9-10 weeks, n=8-9 per group) were randomized into four groups: standard chow 1) with or 2) without noise exposure, losartan-infused chow (20 mg/kg/day) starting 3) three days before noise exposure (pre-exposure treatment group) or 4) immediately after noise exposure (rescue group). Noise exposure consisted of two hours of 8-16k octave band noise at 105dB SPL (males) / 107.5dB SPL (females) to induce permanent threshold shifts. Regimens were changed to standard chow after one month. Auditory brainstem responses (ABR) and Distortion Product Otoacoustic Emission (DPOAE) were recorded before and after one and three months. Group comparisons were performed using the Mann-Whitney U test.

Results: One month after noise exposure, losartan showed a protective effect on ABR threshold shifts (dB SPL) at 8, 16, and 32 kHz in the pre-exposure treatment group compared to the standard control group (55.6 vs. 68.8, 47.5 vs. 61.9, and 51.3 vs. 62.5, respectively, p< 0.05). The rescue group demonstrated even more profound differences (39.4 vs. 68.8, 37.5 vs. 61.9, and 37.5 vs. 62.5, p< 0.05). These differences persisted after three months.
The DPOAE results at 16 kHz for both Losartan-treated groups (pre-exposure and rescue) showed similar protective effects after one and three months. Both groups had significantly lower threshold levels compared to the noise-exposed standard control group (p < 0.01) and no significant difference compared to the no noise-exposed group.

Conclusions: Losartan provides an otoprotective effect against permanent ABR and DPOAE threshold shifts due to noise overexposure, whether used before exposure or started immediately after exposure. Its protective effects persist even after discontinuation of treatment.