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Science Forum Index » Life Extension Forum » Attenuation of progressive hearing loss in a model of...
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| Olafur Pall Olafsson... |
 Posted: Sun May 04, 2008 4:33 pm |
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Brain Res. 2008 Mar 28 [Epub ahead of print]
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Attenuation of progressive hearing loss in a model of age-related
hearing loss by a heat shock protein inducer, geranylgeranylacetone.
Mikuriya T, Sugahara K, Sugimoto K, Fujimoto M, Takemoto T,
Hashimoto M, Hirose Y, Shimogori H, Hayashida N, Inouye S, Nakai A,
Yamashita H.
Department of Otolaryngology, Yamaguchi University Graduate School
of Medicine, Minamikogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan;
Department of Biochemistry and Molecular Biology, Yamaguchi University
Graduate School of Medicine, Japan.
Mechanisms of age-related hearing loss (ARHL) have not been
elucidated as aging processes are extremely complex. Although
oxidative stress and apoptotic cell death are involved in progression
of ARHL, number of trial to treat ARHL is limited. Heat shock response
is characterized by induction of heat shock proteins (HSPs) in
response to stresses such as heat shock, which diminishes during
aging. HSPs act as molecular chaperones, and some HSPs also inhibit
apoptotic pathways. Here, we examined age-related expression of HSPs
in the cochlea of ARHL model DBA/2J mice and control CBA/N mice.
Western blot assay revealed that CBA/N mice showed constant expression
of Hsp70 and Hsp110 with age, but not in DBA/2J mice. The result
suggests that pharmacological upregulation of HSPs might attenuate
ARHL. We administered DBA/2J mice with food containing
geranylgeranylacetone (GGA) that induces HSPs in the cochlea, and
found that its administration suppresses ARHL examined by ABR test and
histological examination though protection is specific for the apical
part of the cochlea. These results demonstrate that dietary
supplementation of GGA could be an effective therapeutic strategy for
treatment of ARHL.
PMID: 18445491 [PubMed - as supplied by publisher]
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* Redox regulation of heat shock protein expression in aging
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nutritional approach. [Amino Acids. 2003]
* Cellular correlates of progressive hearing loss in 129S6/
SvEv mice. [J Comp Neurol. 2004]
* Age-related hearing loss in CD/1 mice is associated to ROS
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Here are two quotes from the full text. The dose used was very high.
"Geranylgeranylacetone (GGA), an acyclic polyisoprenoid, has been used
clinically as an oral anti-ulcer drug since 1984. GGA is easy to cross
the blood–brain barrier because GGA is the lipid-soluble reagent
(announced by interview form Eisai Co., Ltd.). GGA enhances activation
of HSF1 and induces HSPs and shows protective effects in many organs
without any histotoxic effect ([Hirakawa et al., 1996], [Kikuchi et
al., 2002], [Hirota et al., 2000], [Fujiki et al., 2003], [Ishii et
al., 2003], [Mikuriya et al., 2005] and [Otaka et al., 2007])."
GGA granules (as Selbex®; Eisai, Tokyo, Japan) were mixed with
powdered rodent chow at concentrations of 0.5 and 1%, which
corresponding to 400–600 mg/kg/day and 900–1000 mg/kg/day during the
study, respectively (Katsuno et al., 2005). GGA food was administered
to animals from 4 weeks of age until the end of the study." |
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