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

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2020 Jul 10

PMID 32640539

Citations 4

Authors

Yu-Hsuan Wen

Jia-Ni Lin

Rong-Shuan Wu

Szu-Hui Yu

Chuan-Jen Hsu

Guo-Fang Tseng

Hung-Pin Wu

Affiliations

Soon will be listed here.

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--β-d-glucoside (THSG), a bioactive constituent, isolated from 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.

Citing Articles

2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside ameliorates bleomycin-induced pulmonary fibrosis regulating pro-fibrotic signaling pathways.

Huang T, Chen C, Chen L, Lan Y, Huang T, Choo K Front Pharmacol. 2022; 13:997100.

PMID: 36267283 PMC: 9577370. DOI: 10.3389/fphar.2022.997100.

In vitro and in vivo models: What have we learnt about inner ear regeneration and treatment for hearing loss?.

Lee M, Waldhaus J Mol Cell Neurosci. 2022; 120:103736.

PMID: 35577314 PMC: 9551661. DOI: 10.1016/j.mcn.2022.103736.

2,3,4',5‑Tetrahydroxystilbene‑2‑O‑β‑D‑glucoside ameliorates gentamicin‑induced ototoxicity by modulating autophagy via Sesn2/AMPK/mTOR signaling.

Wen Y, Lin H, Lin J, Tseng G, Hwang C, Lin C Int J Mol Med. 2022; 49(5).

PMID: 35348190 PMC: 8989425. DOI: 10.3892/ijmm.2022.5127.

A Review of Pharmacology, Toxicity and Pharmacokinetics of 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-Glucoside.

Wang C, Dai S, Gong L, Fu K, Ma C, Liu Y Front Pharmacol. 2022; 12:791214.

PMID: 35069206 PMC: 8769241. DOI: 10.3389/fphar.2021.791214.

References

Li P, Nijhawan D, Budihardjo I, Srinivasula S, Ahmad M, Alnemri E . Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997; 91(4):479-89. DOI: 10.1016/s0092-8674(00)80434-1. View

Clerici W, Hensley K, DiMartino D, Butterfield D . Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants. Hear Res. 1996; 98(1-2):116-24. DOI: 10.1016/0378-5955(96)00075-5. View

Arslan E, Orzan E, Santarelli R . Global problem of drug-induced hearing loss. Ann N Y Acad Sci. 2000; 884:1-14. DOI: 10.1111/j.1749-6632.1999.tb00277.x. View

Zhou M, Sun G, Zhang L, Zhang G, Yang Q, Yin H . STK33 alleviates gentamicin-induced ototoxicity in cochlear hair cells and House Ear Institute-Organ of Corti 1 cells. J Cell Mol Med. 2018; 22(11):5286-5299. PMC: 6201369. DOI: 10.1111/jcmm.13792. View

Ojano-Dirain C, Antonelli P . Prevention of gentamicin-induced apoptosis with the mitochondria-targeted antioxidant mitoquinone. Laryngoscope. 2012; 122(11):2543-8. DOI: 10.1002/lary.23593. View

Lv G, Lou Z, Chen S, Gu H, Shan L . Pharmacokinetics and tissue distribution of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside from traditional Chinese medicine Polygonum multiflorum following oral administration to rats. J Ethnopharmacol. 2011; 137(1):449-56. DOI: 10.1016/j.jep.2011.05.049. View

Hata K, Kozawa M, Baba K . [A new stilbene glucoside from Chinese crude drug "Heshouwu," the roots of Polygonum multiflorum Thunb (author's transl)]. Yakugaku Zasshi. 1975; 95(2):211-3. DOI: 10.1248/yakushi1947.95.2_211. View

Kucharava K, Sekulic-Jablanovic M, Horvath L, Bodmer D, Petkovic V . Pasireotide protects mammalian cochlear hair cells from gentamicin ototoxicity by activating the PI3K-Akt pathway. Cell Death Dis. 2019; 10(2):110. PMC: 6365508. DOI: 10.1038/s41419-019-1386-7. View

Sun T, Liu H, Cheng Y, Yan L, Krittanawong C, Li S . 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside eliminates ischemia/reperfusion injury-induced H9c2 cardiomyocytes apoptosis involving in Bcl-2, Bax, caspase-3, and Akt activation. J Cell Biochem. 2019; 120(7):10972-10977. DOI: 10.1002/jcb.27949. View

10.

Rybak L, Ramkumar V . Ototoxicity. Kidney Int. 2007; 72(8):931-5. DOI: 10.1038/sj.ki.5002434. View

11.

Zhang W, Wang C, Li F, Zhu W . 2,3,4',5-Tetrahydroxystilbene-2-O-beta-D-glucoside suppresses matrix metalloproteinase expression and inflammation in atherosclerotic rats. Clin Exp Pharmacol Physiol. 2007; 35(3):310-6. DOI: 10.1111/j.1440-1681.2007.04824.x. View

12.

Han X, Ling S, Gan W, Sun L, Duan J, Xu J . 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside ameliorates vascular senescence and improves blood flow involving a mechanism of p53 deacetylation. Atherosclerosis. 2012; 225(1):76-82. DOI: 10.1016/j.atherosclerosis.2012.08.011. View

13.

Jiang P, Ray A, Rybak L, Brenner M . Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti. Otol Neurotol. 2016; 37(9):1449-56. PMC: 5125081. DOI: 10.1097/MAO.0000000000001192. View

14.

Ghashghaei S, Emtiazi G . Increasing the antibacterial activity of gentamicin in combination with extracted polyphosphate from Bacillus megaterium. J Appl Microbiol. 2013; 114(5):1264-72. DOI: 10.1111/jam.12142. View

15.

Rivolta M, Holley M . Cell lines in inner ear research. J Neurobiol. 2002; 53(2):306-18. DOI: 10.1002/neu.10111. View

16.

Heinrich U, Strieth S, Schmidtmann I, Li H, Helling K . Gentamicin alters Akt-expression and its activation in the guinea pig cochlea. Neuroscience. 2015; 311:490-8. DOI: 10.1016/j.neuroscience.2015.10.050. View

17.

Guo C, Sun L, Chen X, Zhang D . Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res. 2014; 8(21):2003-14. PMC: 4145906. DOI: 10.3969/j.issn.1673-5374.2013.21.009. View

18.

Noack V, Pak K, Jalota R, Kurabi A, Ryan A . An Antioxidant Screen Identifies Candidates for Protection of Cochlear Hair Cells from Gentamicin Toxicity. Front Cell Neurosci. 2017; 11:242. PMC: 5563352. DOI: 10.3389/fncel.2017.00242. View

19.

Lee S, Ahn S, Wang Z, Choi Y, Shin H, Choi B . Neuroprotective effects of 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside from Polygonum multiflorum against glutamate-induced oxidative toxicity in HT22 cells. J Ethnopharmacol. 2016; 195:64-70. DOI: 10.1016/j.jep.2016.12.001. View

20.

Setz C, Benischke A, Pinho Ferreira Bento A, Brand Y, Levano S, Paech F . Induction of mitophagy in the HEI-OC1 auditory cell line and activation of the Atg12/LC3 pathway in the organ of Corti. Hear Res. 2018; 361:52-65. DOI: 10.1016/j.heares.2018.01.003. View