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Background: Cisplatin is a chemotherapy drug that can induce sensorineural hearing loss. At present, no otoprotective agent is approved for use.
Objectives: This study investigated the optimal concentration of intratympanic N-acetylcysteine (NAC) to prevent cisplatin-induced ototoxicity in a guinea pig model.
Materials And Methods: Guinea pigs ( = 64) were treated with a single intratympanic injection containing different NAC concentrations or saline (control) 3 days prior to intraperitoneal injection with cisplatin. The threshold change in the auditory brainstem response was assessed.
Results: Four weeks after intraperitoneal cisplatin injection, only the group that received 2% NAC exhibited significant otoprotection ( < .05) compared with the control. Otoprotection was observed at all the frequencies tested (1k, 2k, 4k, and 8k Hz). The 2% NAC group also exhibited significant otoprotection ( < .05) compared with the other NAC groups (at 1k, 2k, 4k, and 8k Hz). The 4% NAC group exhibited significantly reduced hearing capacity ( < .05) in the fourth week compared with controls.
Conclusions And Significance: Intratympanic NAC administration is an efficient and safe means of preventing cisplatin-induced ototoxicity. In our animal model, the optimal intratympanic NAC concentration was 2%; concentrations of 4% loss of otoprotection.
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http://dx.doi.org/10.1080/00016489.2022.2038796 | DOI Listing |
Neurotoxicology
September 2025
Department of Otolaryngology Head and Neck Surgery, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China. Electronic address:
Gadolinium-based contrast agents (GBCAs) are widely used in systemic magnetic resonance imaging (MRI) and can be employed in otology to evaluate endolymphatic hydrops in patients with Ménière's disease. Given the heavy metal properties of gadolinium and its tendency to deposit in tissues, it is essential to assess its ototoxic risk. We evaluated the ototoxicity of gadodiamide using in vitro and in vivo models.
View Article and Find Full Text PDFEur J Pharm Sci
September 2025
Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:
Intratympanic (IT) delivery of dexamethasone (DEX) is widely used for treating inner ear disorders; however, its therapeutic efficacy is limited by poor permeability of the round window membrane (RWM). This study aimed to evaluate and compare the efficacy and safety of three pharmacological agents-histamine (HIS), 3% hypertonic saline (3% HS), and sodium caprate (SC)-as adjuvants for enhancing RWM permeability and improving IT-DEX delivery in a murine model. Following IT administration of each permeability enhancer followed by DEX injection, perilymph DEX concentrations were measured using ultra-high-performance liquid chromatography, and DEX receptor expression in the organ of Corti was assessed by immunofluorescence.
View Article and Find Full Text PDFOtol Neurotol
September 2025
AudioCure Pharma GmbH, Berlin, Germany.
Objective: The objective of this study was to assess the safety and tolerability of the intratympanic delivery of AC102, a novel pharmaceutical therapy based on a thermosensitive gel for preventing and treating a range of hearing impairments, including sudden sensorineural hearing loss. We studied this in healthy, normal-hearing volunteers to evaluate any change in hearing thresholds.
Study Design: An open-label, placebo-controlled, ascending single-dose, multicenter phase 1 clinical trial.
Zhonghua Yi Xue Za Zhi
July 2025
Department of Otolaryngology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
To investigate the protective effect and its mechanism of intratympanic administration of diselenide cross-linked nano-carriers of astaxanthin (AST@dSe-AFT) on vestibular toxicity induced by gentamicin (GM) in mice. Forty-two male ICR mice aged 6-8 weeks were randomly divided into seven groups according to a random number table: control group, GM injury group, natural astaxanthin (AST) protection group (GM+AST group), and four AST@dse-AFT protection groups (GM+AST/NP 0.1 group, GM+AST/NP 1 group, GM+AST/NP 10 group, and GM+AST/NP 100 group), which were given 0.
View Article and Find Full Text PDFTher Deliv
August 2025
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research- Guwahati, Changsari, India.
Background: Drug delivery to perilymph after crossing the round window membrane is paramount important for inner ear disease management. Intratympanic (IT) injection of emulsion-like dispersions augments cinnarizine (CNZ) and morin hydrate (MH)-Lipoid E80 complex permeation into perilymph in a healthy rabbit inner ear model.
Methods: A Box-Behnken design (BBD) followed by artificial neural network (ANN)-linked Levenberg - Marquardt (LM) algorithm was used for optimizing the injection formula.