Geranylgeranylacetone, a heat shock protein inducer, prevents acoustic injury in the guinea pig.
Geranylgeranylacetone (GGA) used widely as anti-ulcer agent is accepted as an inducer of the heat shock proteins (Hsps) at gastric mucosa, liver, heart, and brain. However, there have been no reports that GGA could induce Hsps in the cochlea leading up to the oto-protection. The purpose of the present study was to investigate whether single oral dose of GGA could induce Hsps at cochlea and oral administration had protective effect to the cochlea against noise trauma. We used Hartley guinea pigs and investigated the expression of Hsp70, 40, and 27 in cochlea by Western blot analysis. To evaluate cochlear function, we assessed thresholds of the auditory brain stem response (ABR). For histological assessment, we observed the sensory epithelium using surface preparation technique. GGA (600 mg/kg) or vehicle was given orally to animals. Western blot analysis showed that the expressions of Hsp 70, 40, and 27 were increased 24-48 h after administration of single dose of GGA, whereas there was less expression in the animals given vehicle. In the animals given GGA once a day for a week before sound exposure (130 dB SPL octave band noise with a center frequency of 4 kHz) for 3 h, their ABR threshold elevations were lowered significantly. In addition, significantly fewer defects were observed on outer hair cells of organ of Corti in the animals treated by GGA than those of the animals without GGA. This result shows that pretreatment by GGA have a potential to prevent cochlea damage against the intense noise.
Mikuriya
Takefumi
T
Department of Otolaryngology, Yamaguchi University School of Medicine, Minamikogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan.
Sugahara
Kazuma
K
Takemoto
Tsuyoshi
T
Tanaka
Kuniyoshi
K
Takeno
Kenji
K
Shimogori
Hiroaki
H
Nakai
Akira
A
Yamashita
Hiroshi
H
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015153:Blotting, Western; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D008297:Male; D009622:Noise / Q000009:adverse effects; D013268:Stimulation, Chemical
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D006360:Heat-Shock Proteins; C031049:geranylgeranylacetone