Tauroursodeoxycholic acid attenuates gentamicin-induced cochlear hair cell death in vitro

Jia, Zhanwei; He, Qiang; Shan, Chunguang; Li, Fengyi

doi:10.1016/j.toxlet.2018.05.007

Cited by 24 publications

(19 citation statements)

References 25 publications

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“…According to the previous study of El Mouedden et al, gentamicin treatment caused a higher ratio of apoptosis than other aminoglycosides under the same conditions [ 46 ]. In the present study, like several others [ 16 , 47 , 48 ], we found that gentamicin exposure in UB/OC-2 cells leads to apoptotic cell death ( Figure 1 and Figure 5 ).…”

Section: Discussionsupporting

confidence: 90%

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

Wen

Lin²,

et al. 2020

Molecules

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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.

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Section: Discussionsupporting

confidence: 90%

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

Wen

Lin²,

et al. 2020

Molecules

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“…Through this study, we also found that a higher concentration of TUDCA (1000 μM) was more effective at supporting full-term development without overt abnormalities. Most reports tested lower concentrations, such as 50 μM, and 200 μM TUDCA [ 13 , 14 ], which may be due to the toxicity of TUDCA at 300 μM and above for cultured cells [ 18 ]. Our data also revealed that the toxicity of TUDCA at 1000 μM was observed during IVM but not after IVF.…”

Section: Discussionmentioning

confidence: 99%

Optimizing treatment of tauroursodeoxycholic acid to improve embryonic development after in vitro maturation of cumulus-free oocytes in mice

2018

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Cumulus-free in vitro maturation (IVM) provides a powerful tool to manipulate immature oocytes, but IVM oocytes lead to poor development after fertilization. Supplementation of the culture medium with tauroursodeoxycholic acid (TUDCA), a bile acid, has been reported to improve the development of embryos derived from in vivo fertilized (IVF) embryos after in vitro culture (IVC) by attenuating endoplasmic reticulum stress. However, it remains unclear if TUDCA can improve development of IVM-IVF embryos. Here, we examined whether TUDCA treatment could improve embryonic development during or after IVM. Immature GV oocytes collected from ovaries of ICR female mice that were free from cumulus cells were subjected to IVM in αMEM containing 5% FBS for 16 h. TUDCA was added to the media at varying concentrations (0–1000 μM) during IVM and IVC. TUDCA treatment during IVM reduced both MII and pronuclear (PN) rates but did not affect blastocyst rates of fertilized embryos. In contrast, TUDCA treatment during IVC significantly increased blastocyst formation rates in a concentration dependent manner. Finally, embryo transfer after TUDCA treatment revealed a significant improvement in the rates of offspring production (15% with 1000 μM TUDCA vs. 6.0% control). These results show that treatment with 1000 μM of TUDCA significantly can improve poor embryonic development of cumulus-free IVM-IVF embryos.

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“…TUDCA’s efficacy was also tested in gentamicin induced ototoxicity using both mouse primary OC explant cultures and an OC cell line, HEI-OC1. TUDCA treated samples had significant HC preservation and showed a decrease in iNOS expression (Jia et al, 2018 ). The results of our study are in agreement with these findings showing that TDCA has similar properties to TUDCA whereby it reduces caspase-3, iNOS, and ROS production and thus provides significant otoprotection.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress caused by the generation of ROS and reactive nitrogen intermediates (RNI) has been demonstrated to play a crucial role in sensory cell damage and loss of residual hearing (Jia et al, 2018 ). Extracellular ROS can cause cell death and necrosis by proteolytic degradation and peroxidation of the phospholipids in the cell membrane (Dinh et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Efficacy of Taurodeoxycholic Acid in Providing Otoprotection Using an in vitro Model of Electrode Insertion Trauma

Shah

Mittal

Shahal

et al. 2020

Front. Mol. Neurosci.

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Cochlear implants (CIs) are widely used to provide auditory rehabilitation to individuals having severe to profound sensorineural hearing loss (SNHL). However, insertion of electrode leads to inner trauma and activation of inflammatory and apoptotic signaling cascades resulting in loss of residual hearing in implanted individuals. Pharmaceutical interventions that can target these signaling cascades hold great potential for preserving residual hearing by preventing sensory cell damage. Bile salts have shown efficacy in various regions of the body as powerful antioxidants and anti-inflammatory agents. However, their efficacy against inner ear trauma has never been explored. The objective of this study was to determine whether taurodeoxycholic acid (TDCA), a bile salt derivative, can prevent sensory cell damage employing an in vitro model of electrode insertion trauma (EIT). The organ of Corti (OC) explants were dissected from postnatal day 3 (P-3) rats and placed in serum-free media. Explants were divided into control and experimental groups: (1) untreated controls; (2) EIT; (3) EIT+ TDCA (different concentrations). Hair cell (HC) density, analyses of apoptosis pathway (cleaved caspase 3), levels of reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) activity and Mitochondrial Membrane Potential (MMP) were assayed. Treatment with TDCA provided significant otoprotection against HC loss in a dose-dependent manner. The molecular mechanisms underlying otoprotection involved decreasing oxidative stress, lowering levels of iNOS, and abrogating generation of cleaved caspase 3. The results of the present study suggest that TDCA provides efficient otoprotection against EIT, in vitro and should be explored for developing pharmaceutical interventions to preserve residual hearing post-cochlear implantation.

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Tauroursodeoxycholic acid attenuates gentamicin-induced cochlear hair cell death in vitro

Cited by 24 publications

References 25 publications

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

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

Optimizing treatment of tauroursodeoxycholic acid to improve embryonic development after in vitro maturation of cumulus-free oocytes in mice

Evaluating the Efficacy of Taurodeoxycholic Acid in Providing Otoprotection Using an in vitro Model of Electrode Insertion Trauma

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