Bisdemethoxycurcumin-mediated Attenuation of Apoptosis Prevents Gentamicin-induced Ototoxicity in Mouse Cochlear UB/OC-2 Cells

Ting-Ya Kang; Chuan-Jen Hsu; Jia-Ni Lin; Chen-Chi Wu; Jen-Shu Wang; Hui-Yi Lin; Szu-Hui Yu; Rong-Shuan Wu; Yu-Hsuan Wen; Guo-Fang Tseng; Hung-Pin Wu

doi:10.21873/invivo.12807

Bisdemethoxycurcumin-mediated Attenuation of Apoptosis Prevents Gentamicin-induced Ototoxicity in Mouse Cochlear UB/OC-2 Cells

In Vivo. 2022 May-Jun;36(3):1095-1105. doi: 10.21873/invivo.12807.

Authors

Ting-Ya Kang^#¹, Chuan-Jen Hsu^#^{1

2}, Jia-Ni Lin¹, Chen-Chi Wu^{2

3

4}, Jen-Shu Wang^{5

6}, Hui-Yi Lin⁷, Szu-Hui Yu⁸, Rong-Shuan Wu⁹, Yu-Hsuan Wen^{6

10

11}, Guo-Fang Tseng^{11

12}, Hung-Pin Wu^{13

6

11}

Affiliations

¹ Department of Otolaryngology Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, R.O.C.
² Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan, R.O.C.
³ Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan, R.O.C.
⁴ Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan, R.O.C.
⁵ Department of Chinese Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, R.O.C.
⁶ School of Medicine, Tzu Chi University, Hualien, Taiwan, R.O.C.
⁷ School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
⁸ Department of Music, Tainan University of Technology, Tainan, Taiwan, R.O.C.
⁹ Department of Economics, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
¹⁰ Department of Otolaryngology, Head and Neck Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, R.O.C.
¹¹ Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, R.O.C.
¹² Department of Anatomy, Tzu Chi University, Hualien, Taiwan, R.O.C.
¹³ Department of Otolaryngology Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, R.O.C.; hungpin_wu@yahoo.com.tw.

^# Contributed equally.

Abstract

Background/aim: Gentamicin has been widely prescribed since the last two decades despite its ototoxicity and nephrotoxicity. Bisdemethoxycurcumin (BDMC) is an affordable and safe curcuminoid with medicinal properties. We aimed to understand the effects of BDMC on the gentamicin-induced hair cell damage in mouse cochlear UB/OC-2 cells, in order to elucidate the therapeutic potential of BDMC against gentamicin-induced ototoxicity.

Materials and methods: We quantified the cell membrane potential and examined the regulators and cascade proteins in the intrinsic pathway of hair cell apoptosis. Mouse cochlear UB/OC-2 cells were treated with BDMC before exposure to gentamicin. The effects of BDMC on hair cell viability, mitochondrial function, and apoptosis-related proteins were examined by flow cytometry, western blot, and fluorescent staining.

Results: Our results revealed that BDMC reversed gentamicin-mediated cycle arrest at the G₂/M phase, stabilizing the mitochondrial membrane potential, decreasing cleaved caspase proteins, and successfully reversing hair cell apoptosis.

Conclusion: BDMC is a potential agent for reducing gentamicin-induced ototoxicity.

Keywords: Gentamicin; apoptosis; bisdemethoxycurcumin; mitochondrial function; ototoxicity; reactive oxygen species.

MeSH terms

Animals
Apoptosis
Diarylheptanoids / pharmacology
Gentamicins* / toxicity
Mice
Ototoxicity* / drug therapy
Ototoxicity* / etiology
Ototoxicity* / prevention & control

Substances

Diarylheptanoids
Gentamicins
bisdemethoxycurcumin