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Protective effects of indole-3-propionic acid against TCP-induced hearing loss in mice by mitigating oxidative stress and promoting neutrophil recruitment
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Protective effects of indole-3-propionic acid against TCP-induced hearing loss in mice by mitigating oxidative stress and promoting neutrophil recruitment
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Journal Article
Protective effects of indole-3-propionic acid against TCP-induced hearing loss in mice by mitigating oxidative stress and promoting neutrophil recruitment
2025
Overview
Sensorineural hearing loss (SNHL) poses a significant global health challenge with substantial socioeconomic and medical implications. The pathophysiology involves excessive reactive oxygen species (ROS) in the cochlea, inflammation, cellular apoptosis, etc. Tryptophan metabolite indole-3-propionic Acid (IPA), produced by gut microbiota, may offer therapeutic benefits by modulating inflammation, oxidative stress, and immune responses. However, the roles of IPA in protecting from treatment hearing loss in adult mice
remain
to be investigated. We previously validated that exposure to pesticide metabolite 3, 5, 6-Trichloro-2-pyridinol (TCP) caused hearing loss in mice. Herein, continuous administration of 40 mg/kg IPA for 21 days significantly attenuated the hearing threshold elevation in C57BL/6 mice exposed to 50 mg/kg TCP. IPA treatment reduced the loss of hair cells (HCs) and spiral ganglion neurons (SGNs), preserved nerve fiber
s
, and reversed the damage to spiral ligaments (SL) and stria vascularis (SV). Similarly, IPA cotreatment decreased ROS accumulation in the cochlea and inhibited HC and SGN apoptosis. Transcriptomic analysis showed that IPA enhanced immune responses, particularly through neutrophil recruitment and the activation of regenerative signals like IFNγ. These findings underscore IPA’s protective effects against TCP-induced hearing loss, highlighting the role of immune mechanisms in cochlear protection.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/250
/ 692/308
/ 692/617
/ 692/699
/ Animals
/ Cochlea
/ Hair Cells, Auditory - drug effects
/ Hair Cells, Auditory - metabolism
/ Hearing Loss - chemically induced
/ Hearing Loss, Sensorineural - chemically induced
/ Hearing Loss, Sensorineural - drug therapy
/ Hearing Loss, Sensorineural - prevention & control
/ Humanities and Social Sciences
/ Male
/ Mice
/ Neutrophil Infiltration - drug effects
/ Oxidative Stress - drug effects
/ Reactive Oxygen Species - metabolism
/ Science
