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Objectives/Hypothesis: To examine the effect of hepatocyte growth factor (HGF) for protection of auditory hair cells against aminoglycosides and its molecular mechanisms. Study Design: Experimental study. Methods: We quantitatively assessed protective effects of HGF on mouse cochlear hair cells against neomycin toxicity using explant culture systems. To understand mechanisms of hair cell protection by HGF, we examined the expression of c-Met, HGF receptor, and 4-hydroxynonenal (a lipid peroxidation marker) in the cochlea by means of immunohistochemistry and Western blotting. Results: The application of HGF to cochlear explant cultures significantly reduced the hair cell loss induced by neomycin. Immunohistochemistry showed c-Met expression in normal auditory hair cells, and its increase in response to neomycin-induced damage. Immunostaining for 4-hydroxynonenal suggested that HGF acted by attenuating the lipid peroxidation of auditory epithelia induced by neomycin. Conclusions: These findings demonstrate that a functional HGF/c-Met coupling is present in the cochlea, and HGF application exerts protective effects on hair cells, indicating the potential of HGF as a therapeutic agent for sensorineural hearing loss. Laryngoscope, 2009 [ABSTRACT FROM AUTHOR]

Conclusion: Local application of hepatocyte growth factor using biodegradable gelatin hydrogels attenuates noise-induced hearing loss in guinea pigs. Objectives: To develop an inner ear drug delivery system using gelatin hydrogels that is capable of a sustained delivery of growth factors to the cochlea. We examined the efficacy of the local application of gelatin hydrogels containing hepatocyte growth factor (HGF) in protecting cochlear hair cells from noise-induced damage. Materials and methods: A piece of gelatin hydrogel previously immersed in either HGF or saline was placed on the round window membrane of a guinea pig 1 h after noise exposure (4 kHz octave band noise at 120 dB sound pressure level for 3 h). Auditory function was monitored using auditory brainstem responses (ABRs), and the loss of hair cells was evaluated quantitatively. Results: Local HGF treatment significantly reduced the noise exposure-caused ABR threshold shifts and the loss of outer hair cells in the basal portion of the cochleae. [ABSTRACT FROM AUTHOR]