Protective role of edaravone against cisplatin-induced ototoxicity in an auditory cell line

Im, Gi Jung; Chang, Jiwon; Lee, Se-Hee; Choi, June; Jung, Hak Hyun; Lee, Hyung Min; Ryu, Sung Hoon; Park, Su Kyoung; Kim, Jin Hwan; Kim, Hyung Jong

doi:10.1016/j.heares.2015.08.004

Cited by 18 publications

(8 citation statements)

References 28 publications

(29 reference statements)

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“…in the present study, the auditory Hei-oc1 cell line was used. Following culture with cisplatin, the viability of Hei-oc1 cells was reduced and the apoptotic rate was increased, which was consistent with observations from other studies (34,35).…”

Section: Discussionsupporting

confidence: 92%

Panax�notoginseng Saponins protect auditory cells against cisplatin‑induced ototoxicity by inducing the AKT/Nrf2 signaling‑mediated redox pathway

et al. 2020

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cisplatin-induced cytotoxicity, such as nephrotoxicity, neurotoxicity and ototoxicity, restricts the clinical application of this compound. Panax notoginseng Saponins (PnS) exhibit potent free radical scavenging and antioxidant activity. PnS have been demonstrated to reduce cisplatin-induced nephrotoxicity and neurotoxicity. The present study investigated the ability of PnS to protect the auditory Hei-oc1 cell line against ototoxicity induced by cisplatin. PnS induced activation of the aKT/nuclear factor erythroid 2-related factor 2 (nrf2) signaling pathway. Following pretreatment with PnS, Hei-oc1 cells were treated with cisplatin and cultured for 24 h. The viability of Hei-oc1 cells was examined using a cell counting Kit-8 assay. double staining analysis was used to measure cell apoptosis. The ability of PnS to reduce reactive oxygen species (roS) levels was assessed by flow cytometry. The levels of phosphorylated (p)-aKT, heme oxygenase 1 (Ho-1), nad(P)H quinone dehydrogenase 1 (nQo1), glutamate-cysteine ligase catalytic (Gclc) and nrf2 were measured by western blotting. Hei-oc1 cells that were pretreated with PNS exhibited significantly increased cell viability compared with that noted in cells treated only with cisplatin. in addition, PnS suppressed the induction of apoptosis and roS production following cisplatin treatment. The upregulation of nQo1, Ho-1 and Gclc expression in PnS-pretreated cells was associated with p-aKT levels and the activation of Nrf2. These findings suggested that PnS protected auditory cells against ototoxicity induced by cisplatin by activating aKT/nrf2 signaling. PnS may serve as a potential candidate in regulating cisplatin-induced cytotoxicity.

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Section: Discussionsupporting

confidence: 92%

Panax�notoginseng Saponins protect auditory cells against cisplatin‑induced ototoxicity by inducing the AKT/Nrf2 signaling‑mediated redox pathway

et al. 2020

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“…An animal study demonstrated that EDO injection reduced cardiac biomarkers in isoproterenolinduced myocardial infarction 23 . A lot of studies demonstrated that EDO has anti-necrotic, antiapoptotic, anti-inflammatory cytokine effects on cardiovascular diseases [23][24][25] . EDO restricts the leakage of these biochemical markers, which can be accounted for by Ca +2 channel blockage effect and membrane-stabilizing property 23 .…”

Section: Discussionmentioning

confidence: 99%

Protective effect of edaravone on adriamycin-induced cardiotoxicity in rats

Aygün¹,

Gül²

2019

Cumhuriyet Medical Journal

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Adriamycin (ADR) is an antineoplastic drug that is widely used in chemotherapy but its cardiotoxicity is the most important side effect that limits the clinical use of this drug. In this study, we investigated of edaravone (EDO), which is a potent antioxidant, ADR-induced cardiotoxicity model in rats by electrocardiographic (ECG), biochemical and scintigraphic methods. Methods: Twenty-eight adult male Wistar-Albino rats were randomly separated into four groups; namely control (CON); Adriamycin (ADR); substance control of edaravone (EDO), edaravone + adriamycin (EDO+ADR) groups. Cardiotoxicity in rats was induced by adriamycin injection (cumulative dose:18 mg/kg, intraperitoneal-i.p.-) at an interval of 24 hours (h) on the 5 th , 6 th and 7 th days. Rats receiving edaravone treatment in the adriamycin group administration edaravone (30 mg/kg/day, i.p.) for 7 days and were injected with adriamycin (18 mg/kg, i.p.) on 5 th , 6 th and 7 th days. On the 8 th day electrocardiography (ECG), biochemical and technetium-99m pyrophosphate ( 99m Tc-PYP) scintigraphic parameters were assessed. Results: ADR induction caused changes in the ECG pattern, decreased heartbeat, P wave and QRS complex duration, increased both ST-segment amplitude and QT interval duration (p < 0,001), increase in the biochemical markers [blood urea nitrogen (BUN), creatine kinase (CK), cardiac troponin T (cTnT)], and elevated 99m Tc-PYP uptake level (p < 0,001). EDO treatment prevented all the parameters of ADR-induced cardiotoxicity in rats, by significantly decreased all ADR-associated conduction abnormalities in ECG (p < 0.001), decreased 99m Tc-PYP uptake (p < 0.001) and serum BUN, CK and cTnT, (p < 0.001). Conclusions: Our data demonstrate that EDO has cardioprotective effects on DOX-induced cardiotoxicity. At the same time, this study suggested that 99m Tc-PYP may be using as a non-invasive method for the early diagnosis of ADRinduced cardiotoxicity.

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“…On the other hand, ototoxicity, nephrotoxicity, and neurotoxicity are some of the side effects of cisplatin 51,52 that limit its clinical application. Cisplatin‐induced ototoxicity is one such severe side effect that mainly damages the hair cells of the organ of Corti 53–55 . According to accumulated research, the apoptosis pathway and oxidative stress generated by a damaged antioxidant defense system are strongly associated with cisplatin ototoxicity 56 …”

Section: Discussionmentioning

confidence: 99%

“…Cisplatin-induced ototoxicity is one such severe side effect that mainly damages the hair cells of the organ of Corti. [53][54][55] According to accumulated research, the apoptosis pathway and oxidative stress generated by a damaged antioxidant defense system are strongly associated with cisplatin ototoxicity. 56 Our findings revealed that cisplatin enhances both Gstm1 and Gstt1expression in the cochleae of the CAB/ CaJ mice, and GSTM1 and GSTT1 are members of the GST superfamily, which is involved in phase II detoxification metabolism.…”

Section: Discussionmentioning

confidence: 99%

Gstm1/Gstt1 is essential for reducing cisplatin ototoxicity in CBA/CaJ mice

Liu

Wang

et al. 2022

The FASEB Journal

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Cisplatin is a widely used chemotherapeutic agent. However, its clinical utility is limited because of cisplatin‐induced ototoxicity. Glutathione S‐transferase (GST) was found to play a vital role in reducing cisplatin ototoxicity in mice. Deletion polymorphisms of GSTM1 and GSTT1, members of the GST family, are common in humans and are presumed to be associated with cisplatin‐induced hearing impairment. However, the specific roles of GSTM1 and GSTT1 in cisplatin ototoxicity are not completely clear. Here, under cisplatin treatment, simultaneous deletion of Gstm1 and Gstt1 lead to a more profound hearing loss in CBA/CaJ mice (Gstm1/Gstt1‐DKO) than in wild‐type mice. The Gstm1/Gstt1‐DKO mice, in which phase II detoxification genes were upregulated, exhibited more severe oxidative stress and higher outer hair cell apoptosis in the cochleae than the control mice. Thus, our study revealed that Gstm1 and Gstt1 protect auditory hair cells from cisplatin‐induced ototoxicity in the CBA/CaJ mice, and genetic screening for GSTM1 and GSTT1 polymorphisms could help determine a standard cisplatin dose for cancer patients undergoing chemotherapy.

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Protective role of edaravone against cisplatin-induced ototoxicity in an auditory cell line

Cited by 18 publications

References 28 publications

Panax�notoginseng Saponins protect auditory cells against cisplatin‑induced ototoxicity by inducing the AKT/Nrf2 signaling‑mediated redox pathway

Panax�notoginseng Saponins protect auditory cells against cisplatin‑induced ototoxicity by inducing the AKT/Nrf2 signaling‑mediated redox pathway

Protective effect of edaravone on adriamycin-induced cardiotoxicity in rats

Gstm1/Gstt1 is essential for reducing cisplatin ototoxicity in CBA/CaJ mice

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