Aminoguanidine prevents ototoxicity induced by cisplatin in rats

Abstract

Cisplatin (CDDP) is one of the most potent antineoplastic drugs, but its therapeutic use is limited by side effects such as ototoxicity. This study tested the effect of aminoguanidine (AG), a specific inhibitor of inducible nitric oxide synthase, on CDDP ototoxicity. Female Wistar albino rats were randomly assigned to 4 groups: saline controls (n = 7), CDDP (n = 7), CDDP plus AG (n = 7), and AG (n = 7). Rats in the CDDP group received a single injection of cisplatin (16 mg/kg, ip). Rats in the CDDP plus AG group received aminoguanidine (20 mg/kg, ip) twice daily on the day before and on 5 consecutive days after a single injection of CDDP (16 mg/kg, ip). Rats in the AG group received aminoguanidine (20 mg/ kg, ip) twice daily for 6 days. Distortion product otoacoustic emissions (DPOAEs) were elicited from the control and experimental animals utilizing a standard commercial otoacoustic emissions apparatus. DPOAEs were measured in the rats on day 0, prior to any drug administration, and on day 5. The initial baseline distortion product diagrams (DPgram) and input/output (I/O) function measurements gave similar results in all 4 groups. On day 5, there was significant deterioration of the DPgrams and I/O functions in the CDDP group; no significant changes of DPgrams and I/O functions were observed on day 5 in the other 3 groups. The median amplitudes of DPgrams and I/O functions revealed significant differences between the CDDP group and the other 3 groups. These results suggest that AG had a preventive effect against CDDP ototoxicity. In summary, this study indicates that AG prevents the cochlear dysfunction and hearing loss induced in rats by a single dose of CDDP.