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橙皮苷通过激活 Nrf2 保护耳蜗毛细胞免受顺铂诱导的损伤。

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

机构信息

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, People's Republic of China.

出版信息

Redox Rep. 2024 Dec;29(1):2341470. doi: 10.1080/13510002.2024.2341470. Epub 2024 Apr 17.

DOI:10.1080/13510002.2024.2341470
PMID:38629504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11025410/
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 and 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.

摘要

顺铂在临床肿瘤学中被广泛用作抗癌化疗药物，其严重的耳毒性副作用众所周知。先前的研究表明，活性氧（ROS）的积累在顺铂的内耳毒性中起着关键作用。橙皮苷是从柑橘类水果中提取的一种黄烷酮糖苷，具有抗炎和抗氧化作用。然而，橙皮苷在减轻顺铂诱导的耳毒性方面的确切药理作用仍不清楚。转录因子红细胞生成 2 相关因子 2（Nrf2）是细胞氧化应激反应的关键介质，受橙皮苷的影响。Nrf2 的激活被证明对顺铂诱导的耳毒性具有保护作用。橙皮苷通过激活 Nrf2 减轻顺铂对内耳的不良影响的潜力值得进一步研究。本研究采用 和 顺铂耳毒性模型来探讨这种可能性。我们的结果表明，橙皮苷通过激活感觉毛细胞中的 Nrf2/NQO1 通路减轻顺铂诱导的耳毒性，从而减少 ROS 积累，防止毛细胞凋亡，并减轻听力损失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/c98829cac675/YRER_A_2341470_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/d806afa918d3/YRER_A_2341470_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/1d2d07c0009b/YRER_A_2341470_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/a0db0478da53/YRER_A_2341470_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/1a3e94883dd1/YRER_A_2341470_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/379e13181ac6/YRER_A_2341470_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/7c7f2cef742b/YRER_A_2341470_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/c98829cac675/YRER_A_2341470_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/d806afa918d3/YRER_A_2341470_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/1d2d07c0009b/YRER_A_2341470_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/a0db0478da53/YRER_A_2341470_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/1a3e94883dd1/YRER_A_2341470_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/379e13181ac6/YRER_A_2341470_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/7c7f2cef742b/YRER_A_2341470_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4680/11025410/c98829cac675/YRER_A_2341470_F0007_OC.jpg

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