Natural Product-Based Therapies Against Noise-Induced Hearing Loss
Abstract
Rationale: More than 300 million people worldwide suffer from noise-induced hearing loss. Blast exposure due to artillery gunfire or explosives makes members of the military service particularly susceptible to acoustic trauma. The effects of noise are rapid, with damage to the inner ear occurring within minutes after exposure. Unfortunately, despite the enormous impact of noise-induced hearing loss, the mechanism(s) by which noise induces damage to the inner ear is poorly understood. Moreover, no therapeutic interventions that may help to prevent or alleviate this condition currently exist. Our preliminary studies support the therapeutic potential of piperlongumine to treat hearing loss due to drug toxicity or noise trauma. Piperlongumine is a natural product isolated from the long pepper, Piper Longum, with many beneficial effects such anti-cancer, anti-bacteria, anti-inflammatory and anti-degenerative disorders. Given this and the results presented in this proposal, we want to thoroughly characterize piperlongumine effect in a mouse model for noise trauma. The proposed research meets the intent of the announcement since it will uncover novel therapies against noise-induced hearing loss. Results from this initial work will help to accelerate the identification of therapeutic targets to restore auditory function in affected individuals. Objective: Characterization of piperlongumine as a preventive and therapeutic compound to treat noise-induced hearing loss. Specific Aims. SA 1: To assess the therapeutic effect of piperlongumine against noise trauma. We have evidence suggesting that piperlongumine can protect from antibiotic- and noise-induced hearing loss in both zebrafish and mice. In this aim, we want to further characterize piperlongumine s therapeutic effect. For this purpose, mice will be exposed to two noise levels, one that will result in the loss of the connections between the cells in the inner ear and the neurons, and a second one that will result in the loss of the inner ear cells. Piperlongumine treatment will be initiated after or before the noise stimulus to assess protection and prevention, respectively. The hearing function and the structure of the inner ear will be studied at the end of the experiments. This aim will allow the characterization of piperlongumine s as a compound that can protect from noise damage. SA 2. To assess the mechanism(s) of action of piperlongumine in the inner ear. We are interested in studying how is piperlongumine acting in the inner ear. The goal of this aim is to identify piperlongumine s specific target(s) in the inner ear by using approaches that allow the analysis of multiple molecules at the same time. Animals will be exposed to noise as in SA1, with pre- or post-piperlongumine s treatment. The inner ear will be isolated and processed for the analysis of protein activities. The completion of this aim will direct future efforts toward a better understanding of piperlongumine s mechanism of action in the inner ear and thus, the refinement of piperlongumine s chemical structure to improve its beneficial effect. Altogether, the results presented here raise our enthusiasm toward the successful completion of the present study and the characterization of piperlongumine (and future derivatives) as a putative therapeutic compound that can be used to treat hearing loss due to acoustic trauma. Exposure to damaging noise is still the primary cause for military service-related hearing loss and tinnitus. Estimates by the American Academy of Audiology and the House Committee on Veterans Affairs predict that approximately 21% of U.S. Army Veterans and 60% of Soldiers will show significant hearing impairment. Unfortunately, there is no available treatment for these patients. The short-term impact of this proposal is the characterization of piperlongumine s therapy to treat noise-induced hearing loss in animal models. This will permit further char
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310797
Entities
People
- Marisa Zallocchi
Organizations
- Creighton University
- United States Army