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Geranylgeranylacetone ameliorates acute cochlear damage caused by 3-nitropropionic acid

Kim, Young Ho ; Song, Jae-Jin ; Kim, Young Chul ; Park, Kyung Tae ; Lee, Jin Hee ; Choi, Jong Min ; Lee, Jun Ho ; Oh, Seung-Ha ; Chang, Sun O

Neurotoxicology (Park Forest South), 2010-06, Vol.31 (3), p.317-325 [Periódico revisado por pares]

Amsterdam: Elsevier B.V

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Título:
Geranylgeranylacetone ameliorates acute cochlear damage caused by 3-nitropropionic acid
Autor: Kim, Young Ho ; Song, Jae-Jin ; Kim, Young Chul ; Park, Kyung Tae ; Lee, Jin Hee ; Choi, Jong Min ; Lee, Jun Ho ; Oh, Seung-Ha ; Chang, Sun O
Assuntos: 3-Nitropropionic acid ; Acoustic Stimulation - methods ; Animals ; Auditory Threshold - drug effects ; Biological and medical sciences ; Cochlea ; Cochlear Diseases - chemically induced ; Cochlear Diseases - drug therapy ; Cochlear Diseases - physiopathology ; Disease Models, Animal ; Diterpenes - therapeutic use ; Drug Interactions ; Electroencephalography - methods ; Evoked Potentials, Auditory, Brain Stem - drug effects ; Female ; Fibrocyte ; Gene Expression Regulation - drug effects ; Geranylgeranylacetone ; Guinea Pigs ; Heat shock proteins ; Histamine H2 Antagonists - therapeutic use ; HSP72 Heat-Shock Proteins - metabolism ; Medical sciences ; Nitro Compounds ; Organ of Corti - metabolism ; Organ of Corti - pathology ; Organ of Corti - ultrastructure ; Propionates ; Spiral ganglion cell ; Toxicology
É parte de: Neurotoxicology (Park Forest South), 2010-06, Vol.31 (3), p.317-325
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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Descrição: 3-Nitropropionic acid (3-NP) induces hearing loss by impairing mitochondrial energy generation. Geranylgeranylacetone (GGA) is known to protect the cochlea from various injuries. The present study was designed to investigate the protective effect of GGA against acute 3-NP-induced damage to the cochlear mitochondria. Female Hartley guinea pigs were divided into 4 groups. The 3-NP vehicle was injected to control animals and in animals receiving GGA alone, only GGA was administered for 7 days. 3-NP (500 mM, 4 μl) was administered with (animals receiving both GGA and 3-NP) or without (animals receiving 3-NP alone) GGA pretreatment (800 mg/kg, 7 days). The auditory brainstem response (ABR) was recorded at click and at 8, 16 and 32 kHz before and after injection, respectively. After cochlear harvest, hematoxylin/eosin staining and immunohistochemistry for anti-HSP70 antibody were done. 3-NP exposure resulted in elevated ABR thresholds that exceeded the maximum recording limit, while GGA pretreatment before 3-NP exposure led to a significant decrease in hearing threshold shift. Histological analysis of above former group revealed loss of type II fibrocytes in the spiral ligament, hair cells in the organ of Corti, stellate fibrocytes in the spiral limbus and spiral ganglion cells, while in above latter group, these cells were preserved. Control animals revealed weak HSP70 expression in the nuclei of some supporting cells (pillar cells, Deiters’ cells and Hensen's cells) and interdental cells. Animals receiving GGA alone showed strong HSP70 expression in the same area as in control animals, while animals receiving both GGA and 3-NP demonstrated slightly decreased HSP70 expression in that area. These results suggest that GGA may protect the cochlea against acute injury resulting from mitochondrial dysfunction.
Editor: Amsterdam: Elsevier B.V
Idioma: Inglês

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Geranylgeranylacetone ameliorates acute cochlear damage caused by 3-nitropropionic acid

Kim, Young Ho ; Song, Jae-Jin ; Kim, Young Chul ; Park, Kyung Tae ; Lee, Jin Hee ; Choi, Jong Min ; Lee, Jun Ho ; Oh, Seung-Ha ; Chang, Sun O

Amsterdam: Elsevier B.V

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