Otoprotective Effect of 2,3,4',5-Tetrahydroxystilbene-2- O-β-d-Glucoside on Gentamicin-Induced Apoptosis in Mouse Cochlear UB/OC-2 Cells

  • Molecules. 2020 Jul 6;25(13):3070. doi: 10.3390/molecules25133070.
Yu-Hsuan Wen  1  2 ,  Jia-Ni Lin  3 ,  Rong-Shuan Wu  4 ,  Szu-Hui Yu  5 ,  Chuan-Jen Hsu  3  6 ,  Guo-Fang Tseng  1  7 ,  Hung-Pin Wu  3  8
Affiliations
  • 1. Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan.
  • 2. Department of Otolaryngology, Head and Neck Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan.
  • 3. Department of Otolaryngology, Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan.
  • 4. The Affiliated Senior High School of National Chung Hsing University, Taichung 412011, Taiwan.
  • 5. Department of Music, Tainan University of Technology, Tainan 710302, Taiwan.
  • 6. Department of Otolaryngology, National Taiwan University Hospital, Taipei 100225, Taiwan.
  • 7. Department of Anatomy, Tzu Chi University, Hualien 970374, Taiwan.
  • 8. School of Medicine, Tzu Chi University, Hualien 970374, Taiwan.
PMID: 32640539 DOI: 10.3390/molecules25133070
Abstract

Excessive levels of Reactive Oxygen Species (ROS) lead to mitochondrial damage and apoptotic cell death in gentamicin-induced ototoxicity. 2,3,4',5-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG), a bioactive constituent, isolated from Polygonum multiflorum Thunb., exhibits numerous biological benefits in treating aging-related diseases by suppressing oxidative damage. However, its protective effect on gentamicin-induced ototoxicity remains unexplored. Therefore, here, we aimed to investigate the otoprotective effect of THSG on gentamicin-induced Apoptosis in mouse cochlear UB/OC-2 cells. We evaluated the effect of gentamicin and THSG on the ROS level, superoxide dismutase (SOD) activity, mitochondrial membrane potential, nuclear condensation, and Lactate Dehydrogenase (LDH) release, and the expression of apoptosis-related proteins was assessed to understand the molecular mechanisms underlying its preventive effects. The findings demonstrated that gentamicin increased ROS generation, LDH release, and promoted apoptotic cell death in UB/OC-2 cells. However, THSG treatment reversed these effects by suppressing ROS production and downregulating the mitochondrial-dependent apoptotic pathway. Additionally, it increased the SOD activity, decreased the expression of apoptosis-related proteins, alleviated the levels of the apoptotic cells, and impaired cytotoxicity. To the best of our knowledge, this is the first study to demonstrate that THSG could be a potential therapeutic option to attenuate gentamicin-induced ototoxicity.

Keywords
2,3,4′,5-tetrahydroxystilbene-2-O-β-d-glucoside (THSG); Polygonum multiflorum Thunb.; UB/OC-2 cells; gentamicin; otoprotection; reactive oxygen species (ROS).
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