Pan-caspase inhibitor protects against noise-induced hearing loss in a rodent model
BackgroundDespite the high prevalence of noise-induced hearing loss (NIHL), no effective treatments exist currently. Underlying mechanisms behind NIHL include elevated reactive oxygen species and inflammation, all which ultimately lead to cellular apoptosis. Z-VAD-FMK, an apoptosis inhibitor, has de...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1497773/full |
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| author | Maria Fernanda Yepes Kayla Minesinger Federica M. Raciti Maria Camila Salazar Suhrud M. Rajguru Suhrud M. Rajguru Suhrud M. Rajguru |
| author_facet | Maria Fernanda Yepes Kayla Minesinger Federica M. Raciti Maria Camila Salazar Suhrud M. Rajguru Suhrud M. Rajguru Suhrud M. Rajguru |
| author_sort | Maria Fernanda Yepes |
| collection | DOAJ |
| description | BackgroundDespite the high prevalence of noise-induced hearing loss (NIHL), no effective treatments exist currently. Underlying mechanisms behind NIHL include elevated reactive oxygen species and inflammation, all which ultimately lead to cellular apoptosis. Z-VAD-FMK, an apoptosis inhibitor, has demonstrated protective effects against cochlear hair cells exposed to ototoxic agents; however, its potential for treating NIHL remains unexplored. This study assessed the efficacy of Z-VAD-FMK as a therapeutic for noise-induced cochlear injury in a rodent model.MethodsRodents were assigned to one of four groups: (1) unexposed, (2) noise-exposed, (3) noise + vehicle, and (4) noise + Z-VAD-FMK. Noise delivery consisted of 1 h of 110 dB continuous white-noise, with Z-VAD-FMK administered intraperitoneally 6 h afterward. Auditory brainstem responses (ABRs), cochlear hair cell density, and protein levels were evaluated post-interventions.ResultsNoise exposure caused a permanent threshold shift across all frequencies, with minimal recovery by day 28. However, post-exposure treatment with Z-VAD-FMK significantly mitigated ABR threshold, amplitudes, and latencies shifts particularly at low and mid frequencies. Treatment rescued outer hair cells across middle and basal cochlear turns and reduced caspase-9 and IL-1β levels, as indicated by protein analysis.ConclusionOur findings indicate that a single intraperitoneal injection of Z-VAD-FMK can partially mitigate cochlear dysfunction induced by acoustic overexposure in a rodent model, highlighting its potential as a therapeutic intervention for NIHL. |
| format | Article |
| id | doaj-art-33a523abecf94d2c840bcddc0cee823b |
| institution | Kabale University |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj-art-33a523abecf94d2c840bcddc0cee823b2025-02-10T06:48:51ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-02-011910.3389/fnins.2025.14977731497773Pan-caspase inhibitor protects against noise-induced hearing loss in a rodent modelMaria Fernanda Yepes0Kayla Minesinger1Federica M. Raciti2Maria Camila Salazar3Suhrud M. Rajguru4Suhrud M. Rajguru5Suhrud M. Rajguru6Department of Neuroscience, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Biomedical Engineering, University of Miami, Coral Gables, FL, United StatesDepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Neuroscience, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Biomedical Engineering, University of Miami, Coral Gables, FL, United StatesDepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United StatesBackgroundDespite the high prevalence of noise-induced hearing loss (NIHL), no effective treatments exist currently. Underlying mechanisms behind NIHL include elevated reactive oxygen species and inflammation, all which ultimately lead to cellular apoptosis. Z-VAD-FMK, an apoptosis inhibitor, has demonstrated protective effects against cochlear hair cells exposed to ototoxic agents; however, its potential for treating NIHL remains unexplored. This study assessed the efficacy of Z-VAD-FMK as a therapeutic for noise-induced cochlear injury in a rodent model.MethodsRodents were assigned to one of four groups: (1) unexposed, (2) noise-exposed, (3) noise + vehicle, and (4) noise + Z-VAD-FMK. Noise delivery consisted of 1 h of 110 dB continuous white-noise, with Z-VAD-FMK administered intraperitoneally 6 h afterward. Auditory brainstem responses (ABRs), cochlear hair cell density, and protein levels were evaluated post-interventions.ResultsNoise exposure caused a permanent threshold shift across all frequencies, with minimal recovery by day 28. However, post-exposure treatment with Z-VAD-FMK significantly mitigated ABR threshold, amplitudes, and latencies shifts particularly at low and mid frequencies. Treatment rescued outer hair cells across middle and basal cochlear turns and reduced caspase-9 and IL-1β levels, as indicated by protein analysis.ConclusionOur findings indicate that a single intraperitoneal injection of Z-VAD-FMK can partially mitigate cochlear dysfunction induced by acoustic overexposure in a rodent model, highlighting its potential as a therapeutic intervention for NIHL.https://www.frontiersin.org/articles/10.3389/fnins.2025.1497773/fullNIHLnoise induced hearing losscochleaABRauditory brainstem responsesinner ear therapeutics |
| spellingShingle | Maria Fernanda Yepes Kayla Minesinger Federica M. Raciti Maria Camila Salazar Suhrud M. Rajguru Suhrud M. Rajguru Suhrud M. Rajguru Pan-caspase inhibitor protects against noise-induced hearing loss in a rodent model Frontiers in Neuroscience NIHL noise induced hearing loss cochlea ABR auditory brainstem responses inner ear therapeutics |
| title | Pan-caspase inhibitor protects against noise-induced hearing loss in a rodent model |
| title_full | Pan-caspase inhibitor protects against noise-induced hearing loss in a rodent model |
| title_fullStr | Pan-caspase inhibitor protects against noise-induced hearing loss in a rodent model |
| title_full_unstemmed | Pan-caspase inhibitor protects against noise-induced hearing loss in a rodent model |
| title_short | Pan-caspase inhibitor protects against noise-induced hearing loss in a rodent model |
| title_sort | pan caspase inhibitor protects against noise induced hearing loss in a rodent model |
| topic | NIHL noise induced hearing loss cochlea ABR auditory brainstem responses inner ear therapeutics |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1497773/full |
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