Antioxidant Therapy against Oxidative Damage of the Inner Ear: Protection and Preconditioning

Abstract

Oxidative stress is an important mechanism underlying cellular damage of the inner ear, resulting in hearing loss. In order to prevent hearing loss, several types of antioxidants have been investigated; several experiments have shown their ability to effectively prevent noise-induced hearing loss, age-related hearing loss, and ototoxicity in animal models. Exogenous antioxidants has been used as single therapeutic agents or in combination. Antioxidant therapy is generally administered before the production of reactive oxygen species. However, post-exposure treatment could also be effective. Preconditioning refers to the phenomenon of pre-inducing a preventative pathway by subtle stimuli that do not cause permanent damage in the inner ear. This renders the inner ear more resistant to actual stimuli that cause permanent hearing damage. The preconditioning mechanism is also related to the induction of antioxidant enzymes. In this review, we discuss the mechanisms underlying antioxidant-associated therapeutic effects and preconditioning in the inner ear.

A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology

“…Oxidative stress reduction requires a decrease in ROS or an increase in antioxidant activity. There are the following three mechanisms by which this can be achieved: the upregulation of endogenous antioxidants, introduction of exogenous antioxidants, and ROS-scavenger system promotion [ 77 ]. When addressing hearing loss prevention and management using antioxidants, it is imperative to be addressing multiple aspects of the highly multifaceted pathology.…”

Dual-Specificity Phosphatase 1 (DUSP1) Has a Central Role in Redox Homeostasis and Inflammation in the Mouse Cochlea

“…Oxidative stress and mitochondrial dysfunction are common triggering factors for cochlear degeneration in all scenarios causing SNHL [ 3 ]. Accordingly, a large number of compounds have been tested for their ability to reduce reactive oxygen species (ROS) generation, promote the ROS scavenger system, or enhance cochlear antioxidant defenses Among them, N-acetylcysteine (NAC) is one of the most widely investigated, and it is administered in mice by either intraperitoneal injection or oral gavage (12.5–400 mg/kg) [ 4 , 5 ]. NAC oral intake is approved for human use in the range 200–1200 mg/day [ 4 ].…”

“…Accordingly, a large number of compounds have been tested for their ability to reduce reactive oxygen species (ROS) generation, promote the ROS scavenger system, or enhance cochlear antioxidant defenses Among them, N-acetylcysteine (NAC) is one of the most widely investigated, and it is administered in mice by either intraperitoneal injection or oral gavage (12.5–400 mg/kg) [ 4 , 5 ]. NAC oral intake is approved for human use in the range 200–1200 mg/day [ 4 ]. NAC can stimulate, indirectly, glutathione (GSH) synthesis, acting as L-cysteine precursor, and can also directly break disulfide bonds, acting as a reducing agent [ 6 ].…”

“…We consider that if the redox imbalance was significant, treatment with an antioxidant should prevent hearing loss. NAC was used because its antioxidant properties are well-known and its human use approved [ 4 ]. Therefore, NAC was used as a pharmacological tool to prevent redox imbalance.…”

Effect of Antioxidant Therapy on Oxidative Stress in Vivo

“…In the next contribution, Pak et al [27], starting from the fact that OS is an important mechanism underlying cellular damage of the inner ear resulting in hearing loss, reviewed the mechanisms underlying antioxidant-associated therapeutic effects. Noise exposure, ototoxic drugs, aging, and autoimmune damage seem to trigger inner ear injuries through increased ROS formation.…”