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Updated: Sep 23, 2025
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Pharmacological treatment with annexin A1-derived peptide protects against cisplatin-induced hearing loss
Letícia S Sena1, Gisela R S Sasso1, José Marcos Sanches2
1Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, SP, Brazil.
Abstract:
Cisplatin is an antineoplastic agent widely used, and no effective treatments capable of preventing cisplatin-induced ototoxicity and neurotoxicity in humans have yet been identified. This study evaluated the effect of the anti-inflammatory annexin A1 (AnxA1)-derived peptide Ac2-26 in a cisplatin-induced ototoxicity model. Wistar rats received intraperitoneal injections of cisplatin (10 mg/kg/day) for 3 days to induce hearing loss, and Ac2-26 (1 mg/kg) was administered 15 min before cisplatin administration. Control animals received an equal volume of saline. Hearing thresholds were measured by distortion product otoacoustic emissions (DPOAE) before and after treatments. Pharmacological treatment with Ac2-26 protected against cisplatin-induced hearing loss, as evidenced by DPOAE results showing similar signal-noise ratios between the control and Ac2-26-treated groups. These otoprotective effects of Ac2-26 were associated with an increased number of ganglion neurons compared with the untreated cisplatin group. Additionally, Ac2-26 treatment produced reduced immunoreactivity on cleaved caspase 3 and phosphorylated ERK levels in the ganglion neurons, compared to the untreated group, supporting the neuroprotective effects of the Ac2-26. Our results suggest that Ac2-26 has a substantial otoprotective effect in this cisplatin-induced ototoxicity model mediated by neuroprotection and the regulation of the ERK pathway.
Insights
The anti-inflammatory peptide Ac₂-26 shows promise in preventing cisplatin-induced hearing loss. This study demonstrates its otoprotective and neuroprotective effects in a rat model, offering hope for managing chemotherapy side effects.
Area of Science:
- Pharmacology
- Neuroscience
- Ototoxicology
Background:
- Cisplatin is a vital chemotherapy drug but causes significant ototoxicity and neurotoxicity.
- No effective preventative treatments currently exist for cisplatin-induced hearing loss and nerve damage.
Purpose of the Study:
- To evaluate the otoprotective and neuroprotective potential of the annexin A1 (AnxA1)-derived peptide Ac₂-26 against cisplatin-induced toxicity.
- To investigate the mechanisms underlying Ac₂-26's protective effects.
Main Methods:
- Wistar rats were administered cisplatin to induce ototoxicity and neurotoxicity.
- The peptide Ac₂-26 was administered before cisplatin treatment.
- Hearing function was assessed using distortion product otoacoustic emissions (DPOAE).
- Ganglion neuron counts and levels of cleaved caspase 3 and phosphorylated ERK were analyzed.
Main Results:
- Ac₂-26 treatment significantly protected against cisplatin-induced hearing loss, as indicated by DPOAE results.
- Otoprotection was associated with a higher number of ganglion neurons in Ac₂-26 treated rats.
- Ac₂-26 reduced cleaved caspase 3 and phosphorylated ERK levels in ganglion neurons, suggesting neuroprotection.
Conclusions:
- The Ac₂-26 peptide demonstrates substantial otoprotective effects in a cisplatin-induced ototoxicity model.
- Neuroprotection and regulation of the ERK pathway appear to mediate Ac₂-26's beneficial effects.
- Ac₂-26 represents a potential therapeutic strategy to mitigate cisplatin-induced ototoxicity and neurotoxicity.
