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The first is the antioxidant barrier: polyphenols establish antioxidant defense by activating the Nrf2 signaling pathway, and Nrf2 upregulates the expression of HO-1, SOD-1, NQO-1 and other oxidative genes, so as to increase the number of antioxidant enzymes (SOD/CAT/GPX/GSH), and to neutralize cisplatin-induced reactive oxygen species (ROS) and reactive nitrogen species (RNS)

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3.1.11 Mangiferin (MGF) and pycnogenol Extracted from the genus Mangiferin, MGF protects against cisplatin-associated ototoxicity by down-regulating ROS accumulation, restoring mitochondrial function, and inhibiting apoptosis in in vitro (HEI-OC1 cells and cochlear hair cells) and in vivo (zebrafish larvae and C57BL/6 J mice) models and, the molecular mechanism of which may be attributed to its inhibition of the ROS-MAPK-caspase-3 signalling pathway (Lu et al., 2024)