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

被引:12
作者
Liu, Shuangyue [1 ]
Zhang, Xiao [1 ]
Sun, Meiling [1 ]
Xu, Tao [2 ]
Wang, Aimei [1 ]
机构
[1] Jinzhou Med Univ, Dept Physiol, 40,Sect 3,Songpo Rd, Jinzhou 121000, Liaoning, Peoples R China
[2] Jinzhou Med Univ, Cent Lab, Jinzhou 121000, Liaoning, Peoples R China
关键词
pomegranate peel extract; oxidative stress; forkhead box O3a; ototoxicity; INDUCED OXIDATIVE STRESS; AMINOGLYCOSIDE ANTIBIOTICS; TRANSCRIPTION FACTORS; APOPTOSIS; PROTEINS; PATHWAY; CELLS; ACID; RATS; MICE;
D O I
10.3892/ijmm.2017.3003
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:175 / 181
页数:7
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