Figure 2.

Effects of micronutrients on oxidative stress and cochlea vasculature. (A) Increased ROS generation induced by noise, drugs, aging and even low extracellular Mg²⁺, may lead to oxidative DNA damage and lipid peroxidation in the cell membrane. The non-enzymatic antioxidant system, which is composed by micronutrients such as Vit E, Vit C, and β-Car (metabolized to form Vit A) can block and/or revert lipid peroxidation, by reducing the impact of oxidative stress. (B) In response to ROS overproduction, peroxyl radicals of lipids (LOO·) and alkoxyl radicals of lipids (LO·) can be generated from polyunsaturated fatty acids (PUFA) of the cell membrane phospholipids. Both radicals can be scavenged by Vit E, one of the major antioxidants in the cell membrane. On the other hand, Vit C, considered one of the most important antioxidant molecules in the extracellular fluid, in addition to scavenging ROS, it can also protect cell membranes by regenerating Vit E from the oxidized form (Vit E·). Thus, the functions of both Vit E and Vit C in lipid peroxidation are coupled. Finally, the antioxidant activity of β-Car may also contribute to protect membranes from lipid peroxidation by scavenging LOO·. The reaction product (LO₂-β-Car·) can react in turn with an oxygen molecule to generate a new peroxyl radical (LO₂-β-Car-O₂·). (C) A byproduct of free radical formation in the inner ear (8-Iso-Prostaglandin F₂α) is a powerful vasoconstrictor; and thus reduced blood flow is found with intense noise exposure, which may be blocked by an isoprostane blocker or a cochlear vasodilator, such as Mg²⁺. Similarly Mg²⁺ will increase inner ear blood flow in the vascularly compromised aging ear. Abbreviations: ROS, reactive oxygen species; Vit A, vitamin A; Vit E, vitamin E; Vit C, vitamin C; β-Car, β-Carotene; Mg²⁺, magnesium; O₂·-, superoxide radical; OH·, hydroxyl radicals.