Chapter category: Ischemia-Reperfusion
Superoxide and Acquired Hearing Loss
Chapter authors:
Sandra L. McFadden, Dalian Ding, Edward Lobarinas and Richard J. Salvi
Age-related hearing loss (AHL), noise-induced hearing loss (NIHL), and drug-induced hearing loss (DIHL, or ototoxicity) are the three major types of acquired hearing loss in the adult population. Evidence suggests that cellular damage by reactive oxygen species (ROS) such as the superoxide free radical is a common denominator among them. If so, then pharmacological approaches that target ROS may reduce the incidence and severity of acquired hearing loss. In this chapter, we describe in vitro and in vivo studies that address the role played by superoxide in AHL, NIHL, and DIHL. Our in vitro studies utilized cochlear cultures from C57BL/10J mice. Dose-response curves for hair cell loss were established for gentamicin, an aminoglycoside antibiotic, and cisplatin, a platinum-based anticancer drug. A superoxide dismutase (SOD) mimetic, M40403, provided partial protection from hair cell loss in cultures treated with gentamicin, supporting a primary role of superoxide in its cytotoxicity. In contrast, cultures treated with cisplatin were not protected by M40403, suggesting a different pathway of damage for this ototoxic drug. Our in vivo studies utilized a mutant mouse with a targeted deletion of Sod1, the gene that codes for cytosolic copper/zinc SOD, and chinchillas exposed to high-level noise. SOD-deficient mice developed significantly greater AHL than their wild type littermates, but were generally not more susceptible to NIHL. Consistent with this, chinchillas treated with M40403 during and after noise exposure did not show significant protection compared to untreated controls. Collectively, our studies support a primary role of superoxide in AHL and gentamicin ototoxicity, and suggest that targeting the superoxide radical may limit these forms of acquired hearing loss. NIHL and cisplatin ototoxicity might be clinically amenable to pharmacologic approaches that target ROS other than superoxide or that enhance antioxidants other than SOD.
