Abstract: Objective To study the protective effect of peperphentonamine hydrochloride (PPTA) against gentamicin-induced
cochlear damage and its mechanism to inhibit cell apoptosis. Methods Guinea pigs with normal hearing were randomized into
control, gentamicin, and PPTA treatment groups, and the guinea pigs models of gentamicin-induced cochlear damage received
intraperitoneal injection of PPTA. The changes of hearing of the guinea pigs were evaluated with auditory brainstem response
(ABR) test, and the protein expression of caspase-3 in the cochlear tissue was detected using Western blotting. TUNEL staining,
scanning and transmission electron microscopy were performed to observe the morphological changes of the cochlea. Results
The threshold in ABR in PPTA treatment group was significantly higher than that in the control group (P<0.05) but
significantly lower than that in gentamicin group. Western blotting showed a significantly increased caspase-3 expression in
gentamicin group (P<0.001); caspase-3 expression in PPTA group was obviously higher than that in the control group but
much lower than that in gentamicin group (P<0.001). TUNEL assay and electron microscopy revealed serious damages of the
hair cells in gentamicin group with numerous apoptotic cells in the organ of Corti, stria vascularis and spiral ganglion, and
such cochlear damages were obviously alleviated in PPTA group. Conclusion PPTA can protect against gentamicin-induced
cochlear damage in guinea pigs by decreasing the protein expression of caspase-3 to inhibit cell apoptosis.