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Abbreviations HTY: Hydroxytyrosol (3, 4-dihydroxyphenylethanol) EVOO: Extra virgin olive oil Nrf2: Nuclear factor erythroid 2-related factor 2 NF-B: Nuclear factor kappa-light-chain-enhancer of activated B cells AMPK: AMP-activated protein kinase Keap1: Kelch-like ECH-associated protein 1 ROS: Reactive oxygen species HAT: Hydrogen atom transfer GPX4: Glutathione peroxidase 4 ACSL4: Acyl-CoA synthetase long-chain family member 4 GRAS: Generally recognized as safe EFSA: European food safety authority NOAEL: No-observed-adverse-effect level EC50 / IC50: Half-maximal effective/inhibitory concentration Kd: Dissociation constant ORAC: Oxygen radical absorbance capacity FRAP: Ferric reducing antioxidant power MDA: Malondialdehyde SOD: Superoxide dismutase CAT: Catalase NQO1: NAD(P)H quinone oxidoreductase 1 HO-1: Heme oxygenase 1 LDL: Low-density lipoprotein HDL: High-density lipoprotein TNF-: Tumor necrosis factor alpha IL-1: Interleukin 1 beta eNOS: Endothelial nitric oxide synthase PI3K/Akt/mTOR: Phosphoinositide 3-kinase / protein kinase B MAPK: Mitogen-activated protein kinase HIF1: Hypoxia-inducible factor 1 alpha GPER: G protein-coupled estrogen receptor ERK1/2: Extracellular signal-regulated kinase 1/2 Tmax: Time to maximum plasma concentration Cmax: Maximum plasma concentration HVA: Homovanillic acid DOPAC 3,4: Dihydroxyphenylacetic acid RCT: Randomized controlled trial References Casaburi I, et al

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This finding suggests the body does not recognize AOD9604 as a foreign substance

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Pharmacol Res 117:218227 Rivetti S, Romano A, Mastrangelo S, Attin G, Maurizi P, Ruggiero A (2023) Aminoglycosides-related ototoxicity: mechanisms, risk factors, and prevention in pediatric patients