ABSTRACT
The purpose of this study was to use a murine model to determine if melatonin can protect the inner ear from radiation-induced damage. A total of 81 4-week-old Balb/c mice were randomly divided into five groups: control group; 50 mg/kg melatonin group; 5 mg/kg melatonin+radiotherapy group; 50 mg/kg melatonin+radiotherapy group; radiotherapy group. The radiotherapy groups received 16 Gy irradiation and melatonin was administered by intraperitoneal injection 30 min before radiotherapy. On days 3 and 7 after irradiation the function of outer hair cells was determined by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) testing, pathological changes of inner ear cells were observed by light microscopy, and the expression of prestin mRNA was determined. ABR thresholds were increased and wave I latencies were extended after radiotherapy; however, the increases were lower in the groups that received melatonin (P < 0.05). DPOAEs showed radiotherapy-induced hearing loss at 8-12 kHz, and hearing loss was greater on day 7 than day 3. However, hearing loss was less in the melatonin groups (P < 0.05). Histopathological examination showed irradiation resulted in breaks and distortion of the cochlear basement membrane, disruption of the stria vascularis, and swelling of outer hair cells. Melatonin reduced these changes. Radiotherapy upregulated prestin mRNA expression. Radiotherapy-induced upregulation of prestin was decreased in the melatonin groups (P < 0.05), and the decrease was greater in the 50 mg/kg melatonin group (P < 0.05). Melatonin protects against radiation-induced cochlear damage by reducing damage to outer hair cells.
Subject(s)
Ear, Inner/pathology , Ear, Inner/radiation effects , Melatonin/therapeutic use , Radiation Injuries/drug therapy , Animals , Auditory Threshold/drug effects , Auditory Threshold/radiation effects , Ear, Inner/physiopathology , Evoked Potentials, Auditory, Brain Stem/drug effects , Gene Expression Regulation/drug effects , Gene Expression Regulation/radiation effects , Melatonin/pharmacology , Mice, Inbred BALB C , Molecular Motor Proteins/genetics , Molecular Motor Proteins/metabolism , Otoacoustic Emissions, Spontaneous/drug effects , Otoacoustic Emissions, Spontaneous/radiation effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Radiation Injuries/genetics , Radiation Injuries/physiopathology , Signal-To-Noise RatioABSTRACT
This study aimed to examine expression and microstructural distribution of prestin in outer hair cells, and the effect of dose and time of radiation on prestin expression in the BALB/c mouse. We also investigated the molecular biological characteristics of prestin and possible mechanisms of sensorineural hearing loss caused by radiation. Seventy 4-week-old mice were randomly divided into four groups, including one control group and three experimental groups. Each experimental group was randomly divided into two groups, which were killed to collect specimens of the cochlea on the 3rd and 7th days after exposure to different doses of 8, 12, and 16 Gy radiation. These cochleas were embedded in paraffin, and then cut into sections. The sections were immunostained with anti-prestin antibodies. The distribution of prestin was observed under optical microscopy and the density of prestin-positive expression was quantitatively calculated by Image-Pro Plus. Prestin had high expression in the lateral membrane and low expression in the cytoplasm of outer hair cells above the nucleus. The density of prestin protein expression of the basal turn was not significantly different after exposure to the different doses of radiation compared with the control group, but up-regulation occurred after radiation in the apex turn. We conclude that prestin protein is mainly expressed in the lateral membrane above the nucleus. Prestin protein may be responsible for the mechanism of injury to the inner ear caused by radiation.
