Abstract

OBJECTIVE: To investigate the potential protective effect of recombinant human erythropoietin (rhEPO) against cisplatin-induced ototoxicity.

MATERIALS and METHODS: Twenty-eight Wistar albino rats were divided randomly into four groups, and baseline distortion product otoacoustic emission (DPOAE) responses and auditory brainstem response (ABR) thresholds were obtained. Group I received intraperitoneal (i.p.) saline, Group II received a single dose of i.p. 2000 IU/kg rhEPO, and Group III and Group IV received a single dose of i.p. 16 mg/kg cisplatin injection. In Group IV, 2000 IU/kg rhEPO was also injected intraperitoneally two times: 24 hours before and 30 minutes after i.p. 16 mg/kg cisplatin injection. DPOAEs and ABR measurements were repeated 72 hours following cisplatin administration, and the animals were sacrificed. The cochleae of animals were evaluated histopathologically by light microscopy, and percentage of apoptotic cells in the spiral ganglion was then determined by immunofluorescence analysis.

RESULTS: Post-treatment auditory assessment revealed significant ABR threshold elevations at click and 6 kHz and 8 kHz frequencies in Group III compared to Groups I and II (p<0.05). In Group III, 8 kHz DPOAEs were also significantly deteriorated compared to Groups I and II (p<0.05). In Group IV, the ABR thresholds and DPOAEs were protected at click and 6 kHz; there was no statistically significant difference between Group IV and Group I at those frequencies. Concomitant administration of rhEPO and cisplatin significantly reduced apoptosis and cell damage. The apoptotic cell percentage of spiral ganglions in Group IV was significantly less than in Group III (p=0.01).

CONCLUSION: Our results showed that i.p. application of rhEPO inhibited apoptosis and prevented cisplatin-induced ototoxicity in rats.