Table 2 Potential antioxidants for noise-induced hearing loss
Antioxidants | Mechanisms | Experimental results | Animal models | References |
|---|---|---|---|---|
N-acetylcysteine (NAC) | Provides substrate for GSH synthesis, inhibits the activation of MAPKs pathway, and scavenges free radicals | Effectively attenuates lipid peroxidation in the cochlea of guinea pigs and provides significant protection from hair cell and hearing loss | Noise-exposed guinea pig model (5 h) | Kopke et al. [127] |
Ebselen | Mimics and enhances the activity of GPX1, significantly inhibits ROS and lipid peroxidation, increases the transcriptional activity of ARE and the expression level of HO-1 protein | Significantly reduces ABR threshold shift and loss of OHC in rats | Noise-exposed rat model (4 h) | Alvarado et al. [123] Kim et al. [137] |
Vitamin A | Removes singlet oxygen, prevents lipid peroxidation | Significantly reduces the ABR threshold and protects HCs survival in guinea pigs | Noise-exposed guinea pig model (5 h) | Le Prell et al. [141] |
Vitamin C | Scavenges oxygen free radicals in the aqueous phase, blocks and/or reverts lipid peroxidation in the plasma membrane, regenerates vitamin E from the oxidized form | Significantly reduced PTS and OHCs damage in guinea pigs | Noise-exposed guinea pig model (6 h) | McFadden et al. [148] |
Vitamin E | Inhibits the proliferation cycle of lipid peroxidation by reacting with peroxyl radicals and reducing their quantity | Significantly reduces the ABR threshold and protects HCs survival in guinea pigs | Noise-exposed guinea pig model (5 h) | Le Prell et al. [141] |
Vitamin B12 | Decreases homocysteine levels, leading to increased intracellular glutathione concentrations and inhibiting lipid peroxidation | Surveys based on NIHL patients showed B12 have a significant protective effect on NIHL | Army personnel exposed to military noise | Gok et al. [151] Shemesh et al. [150] |
HK-2 | reduces the oxidative stress generated by free radicals, synthesizes bioactive transition metals including Fe2+, thus reducing their availability to participate in the Fenton reaction that produces highly toxic hydroxyl radicals | reduces noise-induced hearing impairment (reflected in cochlear compound action potential) and hair cell loss in rats | Noise-exposed rat model (8 h/d for 21 days) | Chen et al. [156] |
Qter | As the artificial analog of an endogenous antioxidant coenzyme Q10, involves in free radicals scavenging and regeneration of antioxidants like reduced GSH | Promotes outer hair cell (OHC) survival in a guinea pig NIHL model | Noise-exposed guinea pig model (60 min) | Fetoni et al. [38] |
Folic Acid | Promotes homocysteine metabolism, decreases superoxide metabolism | Folic acid-deficient mice exhibit impaired cochlear homocysteine metabolism and associated oxidative stress | C57BL/6 J female mice (Due to the Ahl alleles present in the C57BL/6 J mouse strain’s genome, these mice demonstrate ARHL from the age of 6 mo onward) | Martínez-Vega et al. [152] |
Acetyl-L carnitine (ALCAR) | Serves as a precursor for L-carnitine, which can shuttle lipid substrates into mitochondria for β-oxidation and enhance ATP production, restores cardiolipin in oxidatively injured cells, further restoring mitochondrial integrity | Significantly reduces hearing threshold shift and loss of OHCs in chinchilla lanigers | Noise-exposed chinchilla laniger model (6 h) | Kopke et al. [39] |