Protective role of quercetin against cisplatin-induced hair cell damage in zebrafish embryos

Lee, S K; Oh, Kyoung Ho; Chung, Ah-Young; Park, H C; Kwon, Soon Young; Choi, June

doi:10.1177/0960327114567766

Cited by 34 publications

(23 citation statements)

References 39 publications

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“…Some of these antioxidants are N-acetyl cysteine (NAC), sodium thiosulfate (STS), amifostine, lipoic acid, resveratrol, intratympanic administration of dexamethasone, intratympanic administration of Ringer lactate, erdosteine, a-tocopherol, chrysin, and quercetin. 1,[12][13][14][15] Especially, antioxidants such as NAC, a-tocopherol, lipoic acid, STS, salicylate, ebselen, D-methionine, and amifostine have been demonstrated to show a protective effect against cisplatin-induced ototoxicity in animal studies and in vitro studies. Clinical studies performed in humans regarding cisplatin-induced ototoxicity are very limited.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Astaxanthin Effect on Cisplatin Ototoxicity in Rats by Using Otoacoustic Emission, Total Antioxidant Capacity, and Histopathological Methods

Kinal¹,

Tatlipinar²,

Uzun³

et al. 2019

Ear Nose Throat J

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Background: Cisplatin-induced ototoxicity is related to oxidative stress. Astaxanthin is one of the most powerful antioxidants in nature. Aims/objectives: To investigate the protective effect of astaxanthin on cisplatin-induced ototoxicity. Materials and Methods: Thirty-five Sprague Dawley female rats were divided into 5 groups: control, cisplatin, and cisplatin with 10, 20, and 40 mg/kg astaxanthin groups. Cisplatin group received a single intraperitoneal injection of 14 mg/kg cisplatin. While saline was administered in the control group, in the other 3 groups, 10, 20, and 40 mg/kg daily doses of astaxanthin were administered through orogastric cannula before administration of cisplatin. Baseline and 10th day otoacoustic emission tests were administered. An intracardiac blood sample was taken to measure total antioxidant capacity (TAC), and the cochleas of the animals were investigated histopathologically. Results: Hearing level of astaxanthin 40 mg/kg þ cisplatin group was higher at 24 kHz and 32 kHz frequencies compared to the cisplatin group. The TAC value of the cisplatin group was lower than both the control and astaxanthin þ cisplatin groups (P < .05). On histopathological examination, the other groups were deformed compared to the control group, but no statistically significant difference was observed between the astaxanthin þ cisplatin and cisplatin groups. Conclusions and significance: Astaxanthin showed protective effect at high frequencies when it was administered at high dose. Thus, astaxanthin may have protective effect against cisplatin-induced ototoxicity.

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Section: Discussionmentioning

confidence: 99%

Investigation of Astaxanthin Effect on Cisplatin Ototoxicity in Rats by Using Otoacoustic Emission, Total Antioxidant Capacity, and Histopathological Methods

Kinal¹,

Tatlipinar²,

Uzun³

et al. 2019

Ear Nose Throat J

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“…The zebrafish were mounted using methylcellulose on a depression slide for evaluation under a fluorescence microscope. We previously reported that all experiments were conducted within 2 h because regeneration itself of hair cells in the zebrafish was not significantly observed during that time after chemicals exposure [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Sodium Selenite Acts as an Otoprotectant against Neomycin-Induced Hair Cell Damage in a Zebrafish Model

et al. 2016

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Sodium selenite is a trace element essential for many physiological functions in the body. It is involved in various biological processes; it acts as a cofactor for antioxidant enzymes that protect against free radicals and is reported to limit metal-mediated oxidative DNA damage. In the present study, we investigated the effect of sodium selenite on neomycin ototoxicity in wild-type and transgenic zebrafish (Brn3C: EGFP). Five or six days post-fertilization, zebrafish larvae were co-exposed to 125 μM neomycin and various concentrations (10 μM, 100 μM, 250 μM, and 500 μM) of sodium selenite for 1 h. Hair cells within neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed by fluorescence microscopy (n = 10 fish per treatment). Hair cell survival was estimated as the ratio of the hair cell numbers in each group compared to those of the control group that were not exposed to neomycin. Apoptosis and hair cell damage of neuromasts were evaluated using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay and 2-[4-(dimethylamino) styryl]-N-ethylpyridinium iodide (DASPEI) assay, respectively. Ultrastructural changes were evaluated using scanning electron microscopy and transmission electron microscopy. Neuromast hair cells were preserved in zebrafish exposed to 125 μM neomycin and 500 μM sodium selenite for 1 h. Sodium selenite protected against neomycin-induced hair cell loss of neuromasts, reduced apoptosis, and prevented zebrafish ultrastructural changes. We propose that sodium selenite protects against neomycin-induced hair cell damage by inhibiting apoptosis, decreasing the disarray of stereocilia, and preventing ultrastructural changes in the neuromast hair cells of the zebrafish.

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“…Zebrafish have proved to be a robust model system for studying cisplatin-mediated hair cell death by monitoring neuromast viability (32,48,62). Moreover, this model has been used to investigate potential otoprotective therapies (46,51,(63)(64)(65)(66)(67)(68)(69). It is however, 5…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4 is activated by platinum and contributes to cisplatin-induced ototoxicity

Babolmorad¹,

Latif²,

Pollock

et al. 2020

Preprint

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Toll-like receptor 4 (TLR4) is famous for recognizing the bacterial endotoxin lipopolysaccharide (LPS) as its canonical ligand. TLR4 is also activated by other classes of agonist including some Group 9/10 transition metals. Roles for these non-canonical ligands in pathobiology mostly remain obscure, though TLR4 interactions with metals 5 can mediate immune hypersensitivity reactions. In this work, we tested whether TLR4 can be activated by the Group 10 transition metal, platinum. We demonstrated that in the presence of TLR4, platinum activates pathways downstream of TLR4 to a similar extent as the known TLR4 agonists LPS and nickel. Platinum is the active moiety in cisplatin, a very potent and invaluable chemotherapeutic used to treat solid tumors in childhood 10 cancer patients. Unfortunately, cisplatin use is limited due to an adverse effect of permanent hearing loss (cisplatin-induced ototoxicity, CIO). Herein, we demonstrated that cisplatin also activates TLR4, prompting the hypothesis that TLR4 mediates aspects of CIO. Cisplatin activation of TLR4 was independent of the TLR4 co-receptors CD14 and MD-2, which is consistent with TLR4 signaling elicited by transition metals. We 15 found that TLR4 is required for cisplatin-induced inflammatory, oxidative and apoptotic responses in an ear outer hair cell line and for hair cell damage in vivo. Thus, TLR4 is a promising therapeutic target to mitigate CIO. We additionally identify a TLR4 small molecule inhibitor able to curtail cisplatin toxicity in vitro. Further work is warranted towards inhibiting TLR4 as a route to mitigating this adverse outcome of childhood 20 cancer treatment. Significance StatementThis work identifies platinum, and its derivative cisplatin, as new agonists for TLR4. TLR4 contributes to cisplatin-induced hair cell death in vitro and in vivo. Genetic and 25 small molecule inhibition of TLR4 identify this receptor as a druggable therapeutic target with promise to curtail cisplatin-induced ototoxicity, a devastating side-effect of an otherwise invaluable chemotherapeutic tool.

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Protective role of quercetin against cisplatin-induced hair cell damage in zebrafish embryos

Cited by 34 publications

References 39 publications

Investigation of Astaxanthin Effect on Cisplatin Ototoxicity in Rats by Using Otoacoustic Emission, Total Antioxidant Capacity, and Histopathological Methods

Investigation of Astaxanthin Effect on Cisplatin Ototoxicity in Rats by Using Otoacoustic Emission, Total Antioxidant Capacity, and Histopathological Methods

Sodium Selenite Acts as an Otoprotectant against Neomycin-Induced Hair Cell Damage in a Zebrafish Model

Toll-like receptor 4 is activated by platinum and contributes to cisplatin-induced ototoxicity

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