Effect of geranylgeranylacetone on gentamycin ototoxicity in rat cochlea culture.
OBJECTIVE
Geranylgeranylacetone (GGA), an anti-ulcer drug, has been reported to induce heat shock proteins (HSPs) in several animal organs. Purpose of this study was to investigate whether GGA has protective effect on gentamycin (GM) ototoxicity and whether it induces HSP70 in rat cochlea.


METHODS
We used cochlea explant culture from postnatal 5-day rat. Explants were pre-incubated with GGA, then incubated with GM and GGA. The number of surviving outer hair cells (OHCs) labeled by phalloidin was counted to evaluate the protective effect of GGA. The expression of HSP70 in whole cochlea tissue was investigated by immunoblot analysis.


RESULTS
The number of surviving OHCs was significantly high in GGA 10(-5)M group compared to GM only group and GGA 10(-6)M group. In the immunoblot analysis, HSP70 levels in GGA added groups were slightly high compared to simple culture group, but much lower than those in heat shock group.


CONCLUSIONS
It was suggested that GGA-induced HSP70, and had partial protective effects on GM ototoxicity in the cochlea. GGA has possibility to be safe and useful treatment drug for cochlea disorder.
Sano
Hajime
H
Department of Otolaryngology, Kitasato University, School of Medicine, 1-15-1 Kitasato, Sagamihra, Kanagawa 228-8555, Japan. sanohj@med.kitasato-u.ac.jp
Yoneda
Satoshi
S
Iwase
Hitoo
H
Itoh
Akihiko
A
Hashimoto
Daimon
D
Okamoto
Makito
M
D000818:Animals; D000831:Animals, Newborn; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003051:Cochlea / Q000378:metabolism*; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D005839:Gentamicins / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects; D015151:Immunoblotting; D051381:Rats; D017208:Rats, Wistar; D046509:Tissue Culture Techniques
D000890:Anti-Infective Agents; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D005839:Gentamicins; D018840:HSP70 Heat-Shock Proteins; C031049:geranylgeranylacetone