FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity

Liu,Shuangyue; Zhang,Xiao; Sun,Meiling; Xu,Tao; Wang,Aimei

doi:10.3892/ijmm.2017.3003

FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity

Authors:
- Shuangyue Liu
- Xiao Zhang
- Meiling Sun
- Tao Xu
- Aimei Wang
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Affiliations: Department of Physiology, Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China, Department of Central Laboratory, Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China
Published online on: May 26, 2017 https://doi.org/10.3892/ijmm.2017.3003
Pages: 175-181
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The use of amikacin (AMK) in present treatment strategies results in severe ototoxicity; however, the underlying molecular mechanisms of this toxicity remain unclear. In this study, we investigated the effectiveness of orally administered pomegranate peel extract (PPE), a strong antioxidant, as a protective agent against AMK-induced ototoxicity. To this end, PPE was orally administered to adult BALB/c mice for 5 days, and the mice were then concurrently treated with AMK (500 mg/kg/day for 15 consecutive days). Auditory threshold shifts induced by AMK were significantly attenuated. The results of immunohistochemical staining and western blot analysis revealed that PPE exerted its protective effects by by downregulating the phosphorylation of Forkhead box O3a (FoxO3a), an important transcription factor which is involved in the responses to oxidative stress. The results also showed that PPE treatment inhibited mitogen-activated protein kinase phosphorylation, prevented the activation of pro-apoptotic protein caspase-3, decreased the levels of apoptosis-inducing Bax protein, and increased the levels of the anti-apoptotic mediator, Bcl-2, induced by AMK in the mouse cochlea. Taken together, our experimental findings suggest that phosphorylated FoxO3a mediates AMK-induced apoptosis in BALB/c mice cochlea. PPE effectively attenuated oxidative stress and ototoxicity by regulating FoxO3a, and may thus prove to be beneficial in protecting auditory cells from ototoxic drugs.

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