期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 46, 期 2, 页码 806-816出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2020.4633
关键词
ursolic acid; cisplatin; cochlea; calcium ion; transient receptor potential vanilloid receptor 1; calpain; 4-hydroxynonenal
资金
- National Natural Science Foundation of China [81674036, 81704127]
- Liaoning Natural Science Foundation [2019-ZD-0832, 20180550402]
- Doctoral Scientific Research Foundation of Liaoning Province [20170520045]
- College Students' Innovation and Entrepreneurship Training Program [201710160000214, 201710160000154, 201910160112]
Cisplatin (CDDP) is widely used in clinical settings for the treatment of various cancers. However, ototoxicity is a major side effect of CDDP, and there is an associated risk of irreversible hearing loss. We previously demonstrated that CDDP could induce ototoxicity via activation of the transient receptor potential vanilloid receptor 1 (TRPV1) pathway and subsequent induction of oxidative stress. The present study investigated whether ursolic acid (UA) treatment could protect against CDDP-induced ototoxicity. UA is a triterpenoid with strong antioxidant activity widely used in China for the treatment of liver diseases. This traditional Chinese medicine is mainly isolated from bearberry, a Chinese herb. The present results showed that CDDP increased auditory brainstem response threshold shifts in frequencies associated with observed damage to the outer hair cells. Moreover, CDDP increased the expression of TRPV1, calpain 2 and caspase-3 in the cochlea, and the levels of Ca(2+)and 4-hydroxynonenal. UA co-treatment significantly attenuated CDDP-induced hearing loss and inhibited TRPV1 pathway activation. In addition, UA enhanced CDDP-induced growth inhibition in the human ovarian cancer cell line SKOV3, suggesting that UA synergizes with CDDPin vitro. Collectively, the present data suggested that UA could effectively attenuate CDDP-induced hearing loss by inhibiting the TRPV1/Ca2+/calpain-oxidative stress pathway without impairing the antitumor effects of CDDP.
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