Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2025, Vol. 39 ›› Issue (3): 11-18.doi: 10.6040/j.issn.1673-3770.0.2025.054

• Shanghai Sixth Peoples Hospital Otorhinolaryngology & Head and Neck Surgery Department dedicated to “120th Anniversary of the Sixth Hospital” Commemorative Theme • Previous Articles     Next Articles

The antagonistic effects of NAD+ on cisplatin-induced oxidative stress injury in hair cells and the regulation of related gene expression

CHEN Ming, KE Bingbing, CUI Yaqi, WU Cuiping, CHEN Zhengnong, LI Chunyan, YIN Shankai   

  1. Department of Otorhinolaryngology & Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
  • Published:2025-06-04

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Abstract: Objective The present study aims to investigate the effect and underlying mechanism of nicotinamide adenine dinucleotide(NAD+). The present study aims to explore the mitigating effect of NAD+ on cisplatin-induced ototoxicity, with a view to elucidating the underlying mechanism. Methods In vitro, HEI-OC1 cells and cochlear basement membrane cultures from 3-day-old C57BL/6J mice were utilized to evaluate the protective effects of NAD+ against cisplatin-induced toxicity. In vivo, the administration of cisplatin and NAD+ was conducted via tympanic injections in adult C57BL/6J mice, followed by auditory brainstem response testing. Transcriptome sequencing was performed to analyze differential gene expression between the cisplatin and cisplatin+ NAD+ groups in HEI-OC1 cells, and the quantitative polymerase chain reaction was applied to validate the key genes. Results The present study investigates the impact of NAD+ on the viability of HEI-OC1 cells exposed to cisplatin, with a particular focus on the phenomenon of apoptosis. The results demonstrate a significant enhancement in cell viability in the presence of NAD+, accompanied by a substantial reduction in apoptosis. In the cochlear basilar membrane model, NAD+ significantly increased hair cell survival and decreased reactive oxygen species(ROS)production. Furthermore, NAD+ effectively mitigated cisplatin-induced hearing loss in vivo. Transcriptome analysis revealed 204 genes to be significantly overexpressed and 214 genes to be significantly underexpressed in the cisplatin + NAD+ group, with differential genes notably enriched in the Platinum drug resistance and Glutathione metabolism pathways. Key genes associated with oxidative stress, drug metabolism, and cyto-protection, such as Gstm6 and Gsta2 were significantly upregulated. Conclusion NAD+ has been demonstrated to possess a protective effect against cisplatin-induced ototoxicity, potentially by modulating the glutathione metabolism pathway in order to counteract oxidative stress. Consequently, these findings imply that NAD+ has therapeutic potential in preventing cisplatin-induced hearing loss.

Key words: Cisplatin, Hair cells, Cochlear basement membrane, Nicotinamide adenine dinucleotide, Reactive oxygen species, Oxidative stress, Hearing impairment

CLC Number: 

  • R764.43
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