Attenuation of noise-induced hearing loss using methylene blue.
The overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been known to contribute to the pathogenesis of noise-induced hearing loss. In this study, we discovered that in BALB/c mice pretreatment with methylene blue (MB) for 4 consecutive days significantly protected against cochlear injury by intense broad-band noise for 3 h. It decreased both compound threshold shift and permanent threshold shift and, further, reduced outer hair cell death in the cochlea. MB also reduced ROS and RNS formation after noise exposure. Furthermore, it protected against rotenone- and antimycin A-induced cell death and also reversed ATP generation in the in vitro UB-OC1 cell system. Likewise, MB effectively attenuated the noise-induced impairment of complex IV activity in the cochlea. In addition, it increased the neurotrophin-3 (NT-3) level, which could affect the synaptic connections between hair cells and spiral ganglion neurons in the noise-exposed cochlea, and also promoted the conservation of both efferent and afferent nerve terminals on the outer and inner hair cells. These findings suggest that the amelioration of impaired mitochondrial electron transport and the potentiation of NT-3 expression by treatment with MB have a significant therapeutic value in preventing ROS-mediated sensorineural hearing loss.
1] Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea [2] Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea [3] Neuroscience Graduate Program, Department of Biological Sciences, Ajou University School of Medicine, Suwon, Korea [4] Chronic inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-380, Korea.
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1] Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea [2] Neuroscience Graduate Program, Department of Biological Sciences, Ajou University School of Medicine, Suwon, Korea [3] Chronic inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-380, Korea.
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1] Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea [2] Neuroscience Graduate Program, Department of Biological Sciences, Ajou University School of Medicine, Suwon, Korea [3] Chronic inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-380, Korea.
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D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D004579:Electron Transport / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D051528:Guanylate Kinases / Q000378:metabolism; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008751:Methylene Blue / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020933:Neurotrophin 3 / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D020933:Neurotrophin 3; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D051528:Guanylate Kinases; D008751:Methylene Blue