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.
