Mouse Model of Cisplatin Induced Ototoxicity / 中山大学学报(医学科学版)

ABSTRACT

@#【Objective】To establish a reliable and reproducible mouse model of cisplatin induced inner ear hair cells loss and to make possible for further study of mechanisms of cisplatin-induced ototoxicity in mice from the molecular and genetic aspects. 【Methods】Twenty healthy mice were evenly divided into two groups in random. The mice in group A received a single dose of furosemide（200 mg/kg，intraperitoneal）followed by a single dose of cisplatin（1.0 mg/kg，intraperitoneal）1 h later，and the mice in group B received a single dose of furosemide（200 mg/kg，intraperitoneal）followed by a single dose of cisplatin（0.5 mg/kg，intraperitoneal）1 h later. Auditory brainstem response（ABR）and distortion product otoacoustic emission （DPOAE） were tested in both groups 10 d post the cisplatin-furosemide treatment and bilateral cochlea were taken out and fixed，one side cochlea were used for the surface preparation of total cochlear basal membrane and stained to count the number of cochlear hair cells from apex to base，the other was embedded with EPON 812 gel and then cut into half thin slices. Six mice were used as control group. 【Results】In both groups，the average ABR threshold of mice at each frequency were elevated，while the average DPOAE values were decreased. The average ABR threshold in group A increased significantly and the amplitude of each frequency decreased a lot，and DPOAE in high frequencies vanished；In group B，there was a minor elevation of ABR threshold with a slightly lower amplitude in higher- frequencies（16，20，32 kHz）but no amplitude change in lower frequencies（4，8，12 kHz）both in ABR and DPOAE. The surface preparation of Cochlear results in group A showed that nearly all the outer hair cells in the base had been destroyed，and most were destroyed in the apex；In group B，only the majority of cochlear outer hair cells at the base missed. There was no decrease of the numbers of the inner hair cells in both groups. Semi-thin cross-sections results also showed that the stria vascularis and spiral ganglion cells were close to normal in both groups. 【Conclusion】Co- administration of single dose of 1.0 mg/kg cisplatin with a single dose of 200 mg/kg furosemide may induce significant loss of cochlear outer hair cells in mice.