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Antioxidative stress-induced damage in cochlear explants
Dalian Ding1,2,3, Jianghui Zhang2, Fang Liu4
1Center for Hearing and Deafness, State University of New York at Buffalo, United States.
Abstract:
The imbalance of reactive oxygen species and antioxidants is considered to be an important factor in the cellular injury of the inner ear. At present, great attention has been placed on oxidative stress. However, little is known about fighting oxidative stress. In the current study, we evaluated antioxidant-induced cochlear damage by applying several different additional antioxidants. To determine whether excessive antioxidants can cause damage to cochlear cells, we treated cochlear explants with 50 μM M40403, a superoxide dismutase mimetic, 50 μM coenzyme Q-10, a vitamin-like antioxidant, or 50 μM d-methionine, an essential amino acid and the important antioxidant glutathione for 48 h. Control cochlear explants without the antioxidant treatment maintained their normal structures after incubation in the standard serum-free medium for 48 h, indicating the maintenance of the inherent oxidative and antioxidant balance in these cochlear explants. In contrast, M40403 and coenzyme Q-10-treated cochlear explants displayed significant hair cell damage together with slight damage to the auditory nerve fibers. Moreover, d-methiodine-treated explants exhibited severe damage to the surface structure of hair cells and the complete loss of the spiral ganglion neurons and their peripheral fibers. These results indicate that excessive antioxidants are detrimental to cochlear cells, suggesting that inappropriate dosages of antioxidant treatments can interrupt the balance of the inherent oxidative and antioxidant capacity in the cell.
Insights
Excessive antioxidants can harm inner ear cells, leading to cochlear damage. This study shows that high doses of antioxidants disrupt the natural oxidative and antioxidant balance, causing hair cell injury.
Area of Science:
- Oto-toxicology
- Cellular Biology
- Biochemistry
Background:
- Oxidative stress, an imbalance between reactive oxygen species and antioxidants, is implicated in inner ear cellular injury.
- While oxidative stress is recognized, the effects of excessive antioxidant use on the inner ear remain under-investigated.
Purpose of the Study:
- To investigate the potential cochlear damage induced by excessive application of various antioxidants.
- To determine if supra-physiological levels of antioxidants can be detrimental to cochlear cells.
Main Methods:
- Cochlear explants were treated with specific antioxidants: M40403 (superoxide dismutase mimetic), coenzyme Q-10, and d-methionine.
- Explants were incubated for 48 hours with 50 μM concentrations of each antioxidant.
- Control explants were maintained in standard serum-free medium to establish baseline structural integrity.
Main Results:
- Treatment with M40403 and coenzyme Q-10 resulted in significant hair cell damage and minor auditory nerve fiber injury.
- d-methionine exposure led to severe damage to hair cell surface structures and complete loss of spiral ganglion neurons and their fibers.
- Control explants retained normal structures, indicating the inherent oxidative and antioxidant balance was maintained.
Conclusions:
- Excessive administration of antioxidants can be detrimental to cochlear cells.
- Inappropriate antioxidant dosages can disrupt the delicate balance of inherent oxidative and antioxidant capacity within cochlear cells, leading to cellular damage.
