Geranylgeranylacetone ameliorates acute cochlear damage caused by 3-nitropropionic acid.
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 microl) 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.
Department of Otolaryngology, Seoul National University, Boramae Medical Center, Seoul, South Korea. yhkiment@gmail.com
Young Ho
YH
Kim
Jae-Jin
JJ
Song
Young Chul
YC
Kim
Kyung Tae
KT
Park
Jin Hee
JH
Lee
Jong Min
JM
Choi
Jun Ho
JH
Lee
Seung-Ha
SH
Oh
Sun O
SO
Chang
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D015834:Cochlear Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use*; D004347:Drug Interactions; D004569:Electroencephalography / Q000379:methods; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D009574:Nitro Compounds; D009925:Organ of Corti / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011422:Propionates
D004224:Diterpenes; D050884:HSP72 Heat-Shock Proteins; D006635:Histamine H2 Antagonists; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid; C031049:geranylgeranylacetone