Protective mechanism of Korean Red Ginseng in cisplatin-induced ototoxicity through attenuation of nuclear factor-κB and caspase-1 activation

Kim,Su‑Jin; Kwak,Hyun  Jeong; Kim,Dae‑Seung; Choi,Hyun‑Myung; Sim,Jung‑Eun; Kim,Sung‑Hoon; Um,Jae‑Young; Hong,Seung‑Heon

doi:10.3892/mmr.2015.3396

Protective mechanism of Korean Red Ginseng in cisplatin-induced ototoxicity through attenuation of nuclear factor-κB and caspase-1 activation

Authors:
- Su‑Jin Kim
- Hyun Jeong Kwak
- Dae‑Seung Kim
- Hyun‑Myung Choi
- Jung‑Eun Sim
- Sung‑Hoon Kim
- Jae‑Young Um
- Seung‑Heon Hong
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Affiliations: Department of Cosmeceutical Science, Daegu Hanny University, Kyungsan 712‑715, Republic of Korea, Department of Pharmacology, College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea, Department of Oriental Pharmacy, College of Pharmacy, Wonkwang‑Oriental Medicines Research Institute, Wonkwang University, Iskan, Jeonbuk 570‑749, Republic of Korea
Published online on: February 27, 2015 https://doi.org/10.3892/mmr.2015.3396
Pages: 315-322

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Abstract

Cisplatin is an effective anti‑cancer drug; however, one of its side effects is irreversible sensorineural hearing damage. Korean Red Ginseng (KRG) has been used clinically for the treatment of various diseases; however, the underlying mechanism of KRG treatment of ototoxicity has not been studied extensively. The present study aimed to further investigate the mechanism of KRG on cisplatin‑induced toxicity in auditory HEI‑OC1 cells in vitro, as well as in vivo. The pharmacological effects of KRG on cisplatin‑induced changes in the hearing threshold of mice were determined, as well as the effect on the impairment of hair cell arrays. In addition, in order to elucidate the protective mechanisms of KRG, the regulatory effects of KRG on cisplatin‑induced apoptosis‑associated gene levels and nuclear factor‑κB (NF‑κB) activation were investigated in auditory cells. The results revealed that KRG prevented cisplatin‑induced alterations in the hearing threshold of mice as well as the destruction of hair cell arrays in rat organ of Corti primary explants. In addition, KRG inhibited cisplatin‑mediated cell toxicity, reactive oxygen species generation, interleukin‑6 production, cytochrome c release and activation of caspases‑3 in the HEI‑OC1 auditory cell line. Furthermore, the results demonstrated that KRG inhibited the activation of NF‑κB and caspase‑1. In conclusion, these results provided a model for the pharmacological mechanism of KRG and provided evidence for potential therapies against ototoxicity.

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