Ursolic acid protects against cisplatin‑induced ototoxicity by inhibiting oxidative stress and TRPV1‑mediated Ca2+‑signaling
Autor: | Shuangyue Liu, Dongyan Bao, Tao Xu, Tingting Ma, Yang Di, Li Yu, Yan Wang, Donghao Qu, Yuan Tian, Aimei Wang, Yuhan Lin |
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Rok vydání: | 2020 |
Předmět: |
inorganic chemicals
0301 basic medicine cochlea Blotting Western TRPV1 cisplatin TRPV Cation Channels transient receptor potential vanilloid receptor 1 Antineoplastic Agents ursolic acid Pharmacology medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ursolic acid Ototoxicity Genetics medicine calcium ion Animals Humans Medicine Chinese Traditional neoplasms Cisplatin Mice Inbred BALB C Oncogene Calpain Caspase 3 Articles General Medicine medicine.disease Immunohistochemistry 4-hydroxynonenal Triterpenes female genital diseases and pregnancy complications Oxidative Stress 030104 developmental biology chemistry Apoptosis 030220 oncology & carcinogenesis Calcium Female Growth inhibition Oxidative stress Signal Transduction medicine.drug |
Zdroj: | International Journal of Molecular Medicine |
ISSN: | 1791-244X 1107-3756 |
Popis: | 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 Ca2+ 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 CDDP in 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. |
Databáze: | OpenAIRE |
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