Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025
Transtympanic Injection of Antioxidant-Eluting Microparticles for Otoprotection From Cisplatin Toxicity in a Mouse Model.
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Smith Eric Michael, Boixo Carmen, Hoffman Larry, Kita Ashley E
Аннотация
OBJECTIVE: Cisplatin is a chemotherapeutic agent with the undesirable side effect of ototoxicity. Transtympanic injections of antioxidant formulations may provide local otoprotection. We tested a novel antioxidant-eluting microparticle for its otoprotective capability from systemic cisplatin as measured by cochlear electrophysiology.
STUDY DESIGN: Basic science.
SETTING: Translational research laboratory.
METHODS: Eighteen mice were assigned to three groups. All mice underwent baseline click-evoked auditory brainstem response (ABR) audiometry and right ear microparticle injections before beginning 42-day intraperitoneal administration regimens of either saline (healthy control empty microparticle [HCEMP] group) or cisplatin (cisplatin empty microparticle [CEMP] group and cisplatin N-acetylcysteine microparticle [CNAC] group). These regimens consisted of three 4-day cycles of intraperitoneal saline or cisplatin administration followed by 10 rest days. HCEMP and CEMP received right-sided transtympanic empty microparticles, and CNAC received transtympanic N-acetylcysteine eluting microparticles. On day 43, all mice underwent posttreatment ABR. ABR thresholds and threshold shifts were analyzed with mixed-effects models and Tukey's post hoc tests and were compared across pretreatment/posttreatment ears, treatment groups, and injected and non-injected ears.
RESULTS: We found that threshold shifts in the ears that received a transtympanic injection of N-acetylcysteine and three cycles of intraperitoneal cisplatin were similar to the paired ears of mice that received no cisplatin. Mice that received a transtympanic injection without N-acetylcysteine and intraperitoneal cisplatin had increased thresholds compared to mice that received a transtympanic injection of N-acetylcysteine and cisplatin.
CONCLUSION: Transtympanic N-acetylcysteine microparticle injections provided functional otoprotection in cisplatin-exposed mice.
STUDY DESIGN: Basic science.
SETTING: Translational research laboratory.
METHODS: Eighteen mice were assigned to three groups. All mice underwent baseline click-evoked auditory brainstem response (ABR) audiometry and right ear microparticle injections before beginning 42-day intraperitoneal administration regimens of either saline (healthy control empty microparticle [HCEMP] group) or cisplatin (cisplatin empty microparticle [CEMP] group and cisplatin N-acetylcysteine microparticle [CNAC] group). These regimens consisted of three 4-day cycles of intraperitoneal saline or cisplatin administration followed by 10 rest days. HCEMP and CEMP received right-sided transtympanic empty microparticles, and CNAC received transtympanic N-acetylcysteine eluting microparticles. On day 43, all mice underwent posttreatment ABR. ABR thresholds and threshold shifts were analyzed with mixed-effects models and Tukey's post hoc tests and were compared across pretreatment/posttreatment ears, treatment groups, and injected and non-injected ears.
RESULTS: We found that threshold shifts in the ears that received a transtympanic injection of N-acetylcysteine and three cycles of intraperitoneal cisplatin were similar to the paired ears of mice that received no cisplatin. Mice that received a transtympanic injection without N-acetylcysteine and intraperitoneal cisplatin had increased thresholds compared to mice that received a transtympanic injection of N-acetylcysteine and cisplatin.
CONCLUSION: Transtympanic N-acetylcysteine microparticle injections provided functional otoprotection in cisplatin-exposed mice.