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In addition, some polyphenols can enhance the anti-tumour effect while antagonizing ototoxicity.Although polyphenols show good application prospects in the prevention and treatment of cisplatin ototoxicity, there are still some problems that need to be solved, such as the low bioavailability of polyphenols, the mechanism of action has not yet been fully elucidated, the optimal dosing regimen has not yet been determined, whether there is any superimposed effect of combining the various types of polyphenols, and whether the oral polyphenols can exert an otoprotective effect through the regulation of the intestinal flora through the intestinal-auricular axis.This study provides new insights into polyphenols as potential drug candidates for CIO by summarising the cytotoxic mechanisms of cisplatin and the mechanism of action of polyphenols targeting these mechanisms in order to retard the progression of CIO

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Besides, OxLDL simultaneously triggers necrosis via ROS [168]

The astroglial syncytial systems, assisted by aquaporin-4 (AQP-4), facilitate the removal of excessive edema fluid from the brain (Rash, Davidson, Yasumura and Furman, 2004)