Hesperidin activates Nrf2 to protect cochlear hair cells from cisplatin-induced damage

ABSTRACT

Cisplatin is widely employed in clinical oncology as an anticancer chemotherapy drug in clinical practice and is known for its severe ototoxic side effects. Prior research indicates that the accumulation of reactive oxygen species (ROS) plays a pivotal role in cisplatin's inner ear toxicity. Hesperidin is a flavanone glycoside extracted from citrus fruits that has anti-inflammatory and antioxidant effects. Nonetheless, the specific pharmacological actions of hesperidin in alleviating cisplatin-induced ototoxicity remain elusive. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical mediator of the cellular oxidative stress response, is influenced by hesperidin. Activation of Nrf2 was shown to have a protective effect against cisplatin-induced ototoxicity. The potential of hesperidin to stimulate Nrf2 in attenuating cisplatin's adverse effects on the inner ear warrants further investigation. This study employs both in vivo and in vitro models of cisplatin ototoxicity to explore this possibility. Our results reveal that hesperidin mitigates cisplatin-induced ototoxicity by activating the Nrf2/NQO1 pathway in sensory hair cells, thereby reducing ROS accumulation, preventing hair cell apoptosis, and alleviating hearing loss.

KEYWORDS:

• Cisplatin
• hesperidin
• Nrf2
• ROS
• apoptosis
• hearing loss
• sensory hair cells
• ototoxicity

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analyzed during the present study appear in the submitted article.

Additional information

Funding

This investigation was supported by grants from the National Natural Science Foundation of China [grant numbers 82201277, 82173154]. We also appreciate the support from the Natural Science Foundation of Guangdong Province [grant numbers 2022A1515012436, 2021A1515010338]. Guangzhou Municipal and University Joint Funding Program [[grant number 202102010340]. The Postdoctoral Research Foundation of China [grant number 2023M734004].