| Objective: To investigate the alterations of hearing function and cochlear morphology following 3,3'-iminodipropionitrile(IDPN) exposure and to explore the ototoxicity of IDPN in guinea pigs. To study the protective effect of ginaton(EGb 761) on IDPN's ototoxicity. Methods: The experiments consist of three parts.The electrophysiological study on hearing function: Fifty guinea pigs were divided into five groups( with 10 animals of each group) and each group are exposed either saline(2ml · kg-1·d-1) or IDPN administered ip. in three consecutive days( dosed at 0, 50, 100, 150, 200 mg· kg-1· d-1). Five animals of each group were chosen at random and the auditory brainstem responses(ABR) were recorded before exposure and 1, 2, 3, 5, 8, 10, 15, 18 days post-exposure. The cochlear microphonics(CM) were recorded in the other five animals of each group two weeks after IDPN exposed.The morphological study on cochlea: Fifteen guinea pigs were divided into three groups( with 5 animals of each group) and were exposed either saline(2ml·kg-1· d-1) or IDPN administered ip. in three consecutive days( dosed at 0, 125, 200 mg · kg-1· d-1). All the animals were decapitated 3 weeks post-exposure for histological assessement. Mid-modiolar sections of cochleas were made in the left ears and observed with light microscope. The right cochleas of each animal were observed with scanning electron microscope(SEM).The protection of EGb 761 on IDPN's ototoxicity: Twenty guinea pigsare divided into two groups( with 10 animals of each group). One groupwere exposed IDPN administered ip. in three consecutive days and the other group were administered EGb 761 for ten consecutive days while exposed the same dosage IDPN. Five animals were chosen at radom and ABR were recorded before exposure and 1, 3, 5, 9, 14, 18 days post-exposure. And then the CM were also recorded at 18 days after exposure. The other five animals of both groups were killed three weeks post-exposure. The morphological indexes were observed with light microscope and SEM in the same way as part II.Results: In the higher dosage groups(150 and 200mg ·kg-1·d-1), the threshold of ABR and CM were elevated and the threshold shift was dose-depend. Latency and amplitude of ABR and CM were changed in 50 mg ·kg-1·d-1 and 100 mg ·kg-1·d-1 group though there were no statistical difference in hearing threshold. The changes of latency and amplitude were also depended on dosage. It were observed that IDPN induced some inside hair cells(IHC) and outside hair cells(OHC) loss(especially OHC) and stereocilia of hair cells(HC) were missing , fused and lost polarity and regularity of arrangement. All of the harm was more serious in higher dosage group(200mg· kg-1· d-1) than in the lower(125mg · kg-1 · d-1) one. There were also a dosage-related loss of spiral ganglion cells(SG) and cochlear nerves(CN). A dosage-related infiltration of inflammatory cell was also observed. Compared to the same IDPN dosage exposure, in the EGb 761 group, the threshold shift of ABR and CM decreased and the impairment of HC, SG and CN was lightened. Conclusion: IDPN can cause dose-depend impairment in hearing function and cochlear morphology in guinea pigs. The use of EGb 761 attenuates the abnormity, suggesting that EGb 761 has protective effect on IDPN's ototoxicity.
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