Abstract
Cisplatin, a widely used chemotherapeutic agent, is associated with a severe side effect called ototoxicity, which can lead to permanent hearing loss. Hesperidin, a flavanone glycoside found in citrus fruits, has been shown to possess otoprotective properties. This article explores the mechanisms through which hesperidin protects cochlear hair cells against cisplatin-induced ototoxicity.
Ototoxicity is a major concern associated with cisplatin therapy. It is caused by the accumulation of cisplatin in the cochlea, leading to oxidative stress and damage to the sensory hair cells. Hesperidin has been reported to protect cochlear hair cells against noise-induced hearing loss and aminoglycoside-induced ototoxicity. However, its effects against cisplatin-induced ototoxicity have not been fully investigated.
Materials and Methods
Adult male Sprague-Dawley rats were used in this study. Cisplatin was administered intraperitoneally to induce ototoxicity. Hesperidin was administered orally before cisplatin treatment. Auditory brainstem response (ABR) thresholds were measured to assess hearing loss. Cochlear tissues were collected for histopathological analysis and biochemical assays.
Results
Hesperidin pretreatment significantly attenuated cisplatin-induced hearing loss, as evidenced by improved ABR thresholds. Histological analysis revealed that hesperidin reduced cisplatin-induced hair cell damage and prevented the loss of spiral ganglion cells. Biochemical assays showed that hesperidin increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates antioxidant defense genes. Hesperidin also increased the levels of antioxidant enzymes, such as glutathione peroxidase and superoxide dismutase, and reduced the levels of reactive oxygen species (ROS).
Discussion
The findings of this study suggest that hesperidin protects cochlear hair cells against cisplatin-induced ototoxicity by inducing Nrf2 activation and enhancing antioxidant defense. Nrf2 is a key regulator of the cellular response to oxidative stress. By increasing Nrf2 expression, hesperidin promotes the transcription of antioxidant genes, leading to increased production of antioxidant enzymes and reduced ROS levels. This antioxidant defense helps to protect cochlear hair cells from cisplatin-induced damage.
Conclusion
Hesperidin has otoprotective effects against cisplatin-induced ototoxicity. Its ability to induce Nrf2 activation and enhance antioxidant defense provides a promising therapeutic strategy for preventing cisplatin-induced hearing loss.
Conflict of Interests
The authors declare no conflict of interests.
Acknowledgements
This study was supported by grants from the National Natural Science Foundation of China (NSFC).
Kind regards,
Dr. R. Naples.
