Zingiberene attenuates paclitaxel-induced ototoxicity by strengthening cochlear antioxidant defense system in vivo

Paclitaxel is widely used in the treatment of many cancers. Paclitaxel-induced ototoxicity is related to the neurotoxic effects of paclitaxel on auditory peripheral neurons. Zingiberene has significant antitumor and antioxidant properties. This study aimed to determine whether zingiberene protects against the ototoxicity caused by paclitaxel. Twenty-four Wistar Albino rats were divided into four groups. The control group received 1 ml/kg saline on days 1, 7, 14, and 21. The paclitaxel group received 5 mg/kg paclitaxel on days 1, 7, 14, and 21. On days 1, 7, 14, and 21, the zingiberene group received 10mg/kg of zingiberene. Paclitaxel + zingiberene group first 5 mg/kg paclitaxel and 30 minutes later 10mg zingiberene on the 1st, 7th, 14th, and 21st days. A distortion product-evoked otoacoustic emission test (DPOAE) was performed before (day 0) and after (day 22) of the experiment. The pretreatment DPOAE values of the groups were not significantly different. On day 22, the DPOAE results in the paclitaxel group showed a considerable decline. Malondialdehyde levels were substantially higher, and glutathione levels were much lower in the paclitaxel group. The paclitaxel+zingiberene group displayed significantly higher DPOAE levels than the paclitaxel group. Compared to the paclitaxel group paclitaxel+zingiberene, glutathione levels were considerably higher, and malondialdehyde levels were significantly lower. The study findings provide the first evidence in the literature that zingiberene can prevent ototoxicity from paclitaxel-induced hearing loss by lowering the levels of oxidant parameters. It demonstrates that administering zingiberene and paclitaxel together may be a practical clinical approach to alleviate paclitaxelinduced ototoxicity.