Statins protect mice from high-decibel noise-induced hearing loss

by Selleckchem | Nov 04 2023

No medical interventions for noise induced hearing loss (NIHL) are approved by the Food and Drug Administration (USA). Here, we evaluate statins in CBA/CaJ mice as potential drugs for hearing loss. Direct delivery of fluvastatin to the cochlea and oral delivery of lovastatin were evaluated. Baseline hearing was assessed using Auditory Brain Stem Responses (ABRs). For fluvastatin, a cochleostomy was surgically created in the basal turn of the cochlea by a novel, laser-based procedure, through which a catheter attached to a mini-osmotic pump was inserted. The pump was filled with a solution of 50 µM fluvastatin+carrier or with the carrier alone for continuous delivery to the cochlea. Mice were exposed to one octave band noise (8-16 kHz x 2 h x 110 dB SPL). In our past work with guinea pigs, fluvastatin protected in the contralateral cochlea. In this study in CBA/CaJ mice, hearing was also assessed in the contralateral cochlea 1-4 weeks after noise exposure. At two weeks post exposure, ABR thresholds at 4, 8, 12, 16, and 32 kHz were elevated, as expected, in the noise+carrier alone treated mice by approximately 9-, 17-, 41-, 29-, and 34-dB, respectively. Threshold elevations were smaller in mice treated with noise+fluvastatin to about 2-, 6-, 20-,12- and 12-dB respectively. Survival of inner hair cell synapses were not protected by fluvastatin over these frequencies. Lovastatin delivered by gavage showed lower threshold shifts than with carrier alone. These data show that direct and oral statin delivery protects mice against NIHL.

Comments:

The provided information describes a study conducted in CBA/CaJ mice to evaluate the potential of statins, specifically fluvastatin and lovastatin, as drugs for noise-induced hearing loss (NIHL). The study aimed to assess the effectiveness of delivering fluvastatin directly to the cochlea and orally administering lovastatin in protecting against NIHL.

To deliver fluvastatin directly to the cochlea, a surgical procedure called cochleostomy was performed in the basal turn of the cochlea using a laser-based method. A catheter attached to a mini-osmotic pump was inserted through the cochleostomy, and the pump was filled with a solution containing 50 µM fluvastatin mixed with a carrier. This setup allowed for continuous delivery of fluvastatin to the cochlea. A control group received the carrier solution alone.

The mice were then exposed to noise at a frequency range of 8-16 kHz for 2 hours at a sound pressure level of 110 dB SPL. One to four weeks after the noise exposure, the mice's hearing was assessed using Auditory Brain Stem Responses (ABRs) in both the exposed cochlea and the contralateral (non-exposed) cochlea. In previous studies with guinea pigs, fluvastatin demonstrated protective effects in the contralateral cochlea, and this study aimed to determine if similar results could be observed in CBA/CaJ mice.

The results showed that in the mice treated with noise and the carrier alone, ABR thresholds at frequencies of 4, 8, 12, 16, and 32 kHz were elevated compared to baseline, as expected for NIHL. The threshold shifts observed were approximately 9 dB, 17 dB, 41 dB, 29 dB, and 34 dB, respectively. In contrast, the mice treated with noise and fluvastatin showed smaller threshold elevations, with shifts of approximately 2 dB, 6 dB, 20 dB, 12 dB, and 12 dB at the same frequencies. These findings suggest that fluvastatin administration provided some protection against NIHL in the mice.

However, it's important to note that the study did not find evidence of fluvastatin protecting the survival of inner hair cell synapses at the tested frequencies. This indicates that while fluvastatin may have reduced the threshold shifts associated with NIHL, it did not fully prevent the damage to the synaptic connections between inner hair cells and auditory nerve fibers.

Additionally, oral administration of lovastatin (gavage) was also evaluated, and the mice treated with lovastatin showed lower threshold shifts compared to the carrier-alone group. This suggests that oral delivery of lovastatin may also provide some degree of protection against NIHL in mice.

Overall, the study suggests that both direct delivery of fluvastatin to the cochlea and oral administration of lovastatin have potential protective effects against NIHL in CBA/CaJ mice. However, further research is needed to fully understand the mechanisms involved and to determine the effectiveness and safety of these interventions in human subjects.