![]() Moreover, some studies have shown that long-term coffee consumption is linked to a lower risk of type 2 diabetes ( Salazar-Martinez et al., 2004 van Dam et al., 2020). (2019) had found that caffeine intake protects against Parkinson’s disease. Thus, preventative treatment and mechanisms of ototoxic drugs have become one of the hot topics in hearing research.Ĭaffeine, as one of the most widely used drugs worldwide, is well known as a major component of common drinks, and it has an incitant effect on the nervous system, stimulating the cerebral cortex and relieving fatigue ( Carolyn Brice, 2001 Mielgo-Ayuso et al., 2019). Additionally, aminoglycoside antibiotics can cause vestibulotoxicity, characterized by vertigo and dizziness, and cochleotoxicity. Previous studies have confirmed that cisplatin damages hair cells, spiral neurons, supporting cells, and vascular veins ( Gao D. Different drugs may damage different parts of the cochlea. Some general therapeutic drugs, such as antineoplastic drugs and aminoglycosides, directly kill inner ear cells, ultimately leading to serious hearing loss ( He et al., 2015 Liu et al., 2016 Zhang et al., 2017 Li et al., 2018). Thus, it is urgent to identify an effective method to prevent or improve hearing loss.įor all the reasons leading to hearing loss, ototoxic drugs are regarded as the major preventable factors ( Liu W. There are still a substantial number of people suffering from cureless hearing loss. However, the effect of these clinical treatments is limited. Medical therapy, surgery, amplification, or hearing implants have been used to improve the threshold ( Lee and Bance, 2019). The clinical treatment of hearing loss depends on the cause and type of hearing loss. Hearing loss is closely associated with decreased quality of life, especially by impacting speech and language development in children and causing social problems for adults ( Lasak et al., 2014). Societal changes have made hearing loss more common owing to excessive exposure to loud noise and ototoxic drugs being more common ( Brown et al., 2018). Additionally, our findings provided new insights into ototoxic drugs, demonstrating that SGK1 and its downstream pathways may be potential therapeutic targets for hearing research at the molecular level.Īccording to the WHO’s report on hearing, more than 1.5 billion people now suffer from hearing loss worldwide, and nearly 2.5 billion people will be living with different degrees of hearing loss by 2050. Together, these results indicated that caffeine induces autophagy and apoptosis in auditory hair cells via the SGK1/HIF-1α pathway, suggesting that caffeine may cause hearing loss. Western blot analysis suggested that GSK650394 and CoCl 2 relieved the caffeine-induced apoptosis and autophagy. ![]() To confirm the role of SGK1 and HIF-1α, GSK650394 was used as an inhibitor of SGK1 and CoCl 2 was used as an inducer of HIF-1α. We verified the interaction between SGK1 and HIF-1α by co-IP. The results of flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting showed that caffeine caused autophagy and apoptosis via SGK1 pathway. To confirm our observations in vitro, we used the HEI-OC1 cell line, a cochlear hair cell-like cell line, to investigate the role of caffeine in hearing loss. RNA-seq results suggested that SGK1 might play a vital role in ototoxicity. In vivo research showed that 120 mg/ kg caffeine injection caused hearing loss by damaging the organ of Corti, stria vascularis, and spiral ganglion neurons. ![]() ![]() Flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting were performed to detect the effects of SGK1 in HEI-OC1 cells and basilar membranes. A CCK-8 assay was used to evaluate the approximate concentration of caffeine. RNA sequencing was conducted to profile mRNA expression differences in the cochlea of control and caffeine-treated mice. First, we explored the difference in auditory brainstem response (ABR), organ of Corti, stria vascularis, and spiral ganglion neurons between the control and caffeine-treated groups of C57BL/6 mice. However, it is unknown whether caffeine causes hearing loss, and there is great interest in determining the effect of caffeine in cochlear hair cells. Caffeine is known as a mild stimulant of the central nervous system, which is also closely related to neurologic disease. Departments of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of University of Science and Technique of China, Hefei, ChinaĬaffeine is being increasingly used in daily life, such as in drinks, cosmetics, and medicine.Xiaomin Tang Yuxuan Sun Chenyu Xu Xiaotao Guo Jiaqiang Sun Chunchen Pan* Jingwu Sun*
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