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Biochem Biophys Res Commun. 2014 Jun 27;449(2):183-9. doi: 10.1016/j.bbrc.2014.04.118. Epub 2014 May 2.

Alpha-lipoic acid protects against cisplatin-induced ototoxicity via the regulation of MAPKs and proinflammatory cytokines.

Author information

1
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Daegu, Republic of Korea.
2
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
3
Vestibulocochlear Research Center, Center for Metabolic Function Regulation and Department of Microbiology, Wonkwang University School of Medicine, Iksan, Jeonbuk, Republic of Korea.
4
Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
5
Department of Internal Medicine, Research Institute of Aging and Metabolism, World Class University Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
6
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Daegu, Republic of Korea. Electronic address: kimuk@knu.ac.kr.
7
Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: kylee@knu.ac.kr.

Abstract

Cisplatin is an effective antineoplastic drug that is widely used to treat various cancers; however, it causes side effects such as ototoxicity via the induction of apoptosis of hair cells in the cochlea. Alpha-lipoic acid (ALA) has been reported to exert a protective effect against both antibiotic-induced and cisplatin-induced hearing loss. Therefore, this study was conducted to (1) elucidate the mechanism of the protective effects of ALA against cisplatin-induced ototoxicity using in vitro and ex vivo culture systems of HEI-OC1 auditory cells and rat cochlear explants and (2) to gain additional insight into the apoptotic mechanism of cisplatin-induced ototoxicity. ALA pretreatment significantly reduced apoptotic cell death of the inner and outer hair cells in cisplatin-treated organ of Corti explants and attenuated ototoxicity via marked inhibition of the increase in the expression of IL-1β and IL-6, the phosphorylation of ERK and p38, the degradation of IκBα, the increase in intracellular levels of ROS, and the activation of caspase-3 in cisplatin-treated HEI-OC1 cells. This study represents the first histological evaluation of the organ of Corti following treatment with ALA, and these results indicate that the protective effects of ALA against cisplatin-induced ototoxicity are mediated via the regulation of MAPKs and proinflammatory cytokines.

KEYWORDS:

Alpha-lipoic acid; Cisplatin; Cochlear explant; MAPKs; Ototoxicity; Proinflammatory cytokines

PMID:
24796665
DOI:
10.1016/j.bbrc.2014.04.118
[Indexed for MEDLINE]

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