In vitro effects of hydrogen peroxide on the cochlear neurosensory epithelium of the guinea pig.
Reactive oxygen species (ROS) have been postulated to be involved in drug ototoxicity and noise-induced hearing loss. Hydrogen peroxide (H(2)O(2))-induced cell damage in the inner ear was investigated using the neurosensory epithelium of a guinea pig cochlea. Hair cells and supporting cells of the epithelium incubated in Hanks' balanced salt solution were viable up to 6 h. After 2 h of treatment with 0.2 mM H(2)O(2) about 85% of the outer hair cells lost their viability. In contrast inner hair cells slowly began to die after 2 h of H(2)O(2) treatment. The Deiters cells and Hensen cells did not show any signs of damage in the presence of H(2)O(2). Nifedipine, a calcium channel blocker, Quin-2 AM, an intracellular calcium chelator, and 2,2'-dipyridyl, a membrane-permeable iron chelator, all provided partial protection against H(2)O(2)-induced outer hair cell death. The combination of both chelators showed an additional protective effect. The antioxidants N-acetylcysteine and glutathione-monoethyl ester completely protected against H(2)O(2) damage. These results suggest that calcium, iron, and thiol homeostasis play a crucial role in hair cell death caused by H(2)O(2).
Dehne
N
N
Department of Otorhinolaryngology, University of Essen, Hufelandstr. 55, 45122, Essen, Germany.
Lautermann
J
J
ten Cate
W J
WJ
Rauen
U
U
de Groot
H
H
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003051:Cochlea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000502:physiology; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D018696:Neuroprotective Agents / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D013997:Time Factors
D000634:Aminoquinolines; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D018696:Neuroprotective Agents; D015082:2,2'-Dipyridyl; C035738:Quin2-acetoxymethyl ester; D006861:Hydrogen Peroxide; D009543:Nifedipine