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Studies over the last decade have left little doubt that reactive oxygen species (ROS) participate in the cellular events leading to aminoglycoside-induced hearing loss. The evidence ranges from the demonstration of aminoglycoside-mediated ROS formation in vitro to the prevention of ototoxicity by antioxidants in guinea pig in vivo. Here we review a(More)
The mammalian inner ear loses its sensory cells with advancing age, accompanied by a functional decrease in balance and hearing. This study investigates oxidant stress in the cochlea of aging male CBA/J mice. Glutathione-conjugated proteins, markers of H2O2-mediated oxidation, began to increase at 12 months of age; 4-hydroxynonenal and 3-nitrotyrosine,(More)
Antioxidant therapy protects against aminoglycoside-induced ototoxicity in animal models. A clinically suitable antioxidant must not affect the therapeutic efficacy of aminoglycosides or exhibit any side effects of its own. In addition, the treatment should be inexpensive and convenient in order to be implemented in developing countries where the use of(More)
Salicylate has recently been demonstrated to protect against the auditory and vestibular side effects of aminoglycoside antibiotics. Similarities in the toxic mechanisms suggest salicylate as a treatment strategy to prevent the ototoxic side effects of cisplatin (CDDP). We first tested protection of the inner ear in Wistar rats receiving a single infusion(More)
We have previously reported the activation of cell death pathways in the sensory cells of the aging cochlea. Here we investigate age-associated changes in survival mechanisms focusing on phosphatidylinositol 3,4,5-trisphosphate (PIP(3))/Akt signaling. The animal model is the CBA/J mouse of 18 months of age prior to the onset of major functional loss (ABR(More)
Cell death in outer hair cells of the mammalian inner ear induced by aminoglycoside antibiotics is mediated by reactive oxygen species (ROS) and can be prevented by antioxidants. The current study investigates the role of the nuclear factor (NF)-kappaB pathway in cell death or survival in adult CBA mice. Kanamycin (700 mg/kg subcutaneously, twice per day)(More)
Oxidative stress has been linked to noise- and drug-induced as well as age-related hearing loss. Antioxidants can attenuate the decline of cochlear structure and function after exposure to noise or drugs, but it is debated as to whether they can protect from age-related hearing loss. In a long-term longitudinal study, 10-month-old female CBA/J mice were(More)
Aminoglycoside antibiotics and cisplatin (CDDP) are the major ototoxins of clinical medicine due to their capacity to cause significant and permanent hearing loss by targeting the mammalian sensory cells. Understanding the pathogenesis of damage is the first step in designing effective prevention of drug-induced hearing loss. In-vitro systems greatly(More)
Commercially obtained aged male CBA/J mice presented a complex pattern of hearing loss and morphological changes. A significant threshold shift in auditory brainstem responses (ABR) occurred at 3 months of age at 4 kHz without apparent loss of hair cells, rising slowly at later ages accompanied by loss of apical hair cells. A delayed high-frequency deficit(More)
Aminoglycosides are potent antibacterials, but therapy is compromised by substantial toxicity causing, in particular, irreversible hearing loss. Aminoglycoside ototoxicity occurs both in a sporadic dose-dependent and in a genetically predisposed fashion. We recently have developed a mechanistic concept that postulates a key role for the mitochondrial(More)