Abstract: Objective To investigate the effect of amikacin (AMK) on the expression of phosphorylated JNK (p-JNK) in hair cells of guinea pig cochlea and the mechanism of AMK ototoxicity. Methods Guinea pigs were assigned to control group, AMK 3, 7 and 11 days group. Animals from AMK groups were daily received intramuscular injection of AMK (400 mg/kg) , while control animals were received an equivalent volume of saline. Auditory brainstem response (ABR) test and tetramethylrhodamine isothiocyanate (TRITC) -labeled phalloidine staining were used to observe the auditory function and hair cells morphology. immunohistochemistry and imaging analysis technique and Western blot were used to detect the expression of p-JNK in the cochlea. Results The hair cells missing was increased in the basal turn of cochlea and developed to the second turn. The expression of p-JNK was greater remarkably in AMK groups. And the ABR thresholds shifts increase significantly than the control group (P＜0.01) . Conclusion JNK signal pathway might participate in AMK- induced ototoxicity.

Key words: c-Jun N-terminal kinase, Amikacin, Guinea pig, Cochlea