Fursultiamine Prevents Drug-Induced Ototoxicity by Reducing Accumulation of Reactive Oxygen Species in Mouse Cochlea
Drug-induced hearing loss is a major type of acquired sensorineural hearing loss. Cisplatin and aminoglycoside antibiotics have been known to cause ototoxicity, and excessive accumulation of intracellular reactive oxygen species (ROS) are suggested as the common major pathology of cisplatin- and ami...
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MDPI AG
2021-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/10/1526 |
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| author | Ye-Ri Kim Tae-Jun Kwon Un-Kyung Kim In-Kyu Lee Kyu-Yup Lee Jeong-In Baek |
| author_facet | Ye-Ri Kim Tae-Jun Kwon Un-Kyung Kim In-Kyu Lee Kyu-Yup Lee Jeong-In Baek |
| author_sort | Ye-Ri Kim |
| collection | DOAJ |
| description | Drug-induced hearing loss is a major type of acquired sensorineural hearing loss. Cisplatin and aminoglycoside antibiotics have been known to cause ototoxicity, and excessive accumulation of intracellular reactive oxygen species (ROS) are suggested as the common major pathology of cisplatin- and aminoglycoside antibiotics-induced ototoxicity. Fursultiamine, also called thiamine tetrahydrofurfuryl disulfide, is a thiamine disulfide derivative that may have antioxidant effects. To evaluate whether fursultiamine can prevent cisplatin- and kanamycin-induced ototoxicity, we investigated their preventive potential using mouse cochlear explant culture system. Immunofluorescence staining of mouse cochlear hair cells showed that fursultiamine pretreatment reduced cisplatin- and kanamycin-induced damage to both inner and outer hair cells. Fursultiamine attenuated mitochondrial ROS accumulation as evidenced by MitoSOX Red staining and restored mitochondrial membrane potential in a JC-1 assay. In addition, fursultiamine pretreatment reduced active caspase-3 and TUNEL signals after cisplatin or kanamycin treatment, indicating that fursultiamine decreased apoptotic hair cell death. This study is the first to show a protective effect of fursultiamine against cisplatin- and aminoglycoside antibiotics-induced ototoxicity. Our results suggest that fursultiamine could act as an antioxidant and anti-apoptotic agent against mitochondrial oxidative stress.in cochlear hair cells. |
| first_indexed | 2024-03-10T06:46:49Z |
| format | Article |
| id | doaj.art-f2650db040cc4ed6a0637364de6b2d07 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T06:46:49Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-f2650db040cc4ed6a0637364de6b2d072023-11-22T17:15:19ZengMDPI AGAntioxidants2076-39212021-09-011010152610.3390/antiox10101526Fursultiamine Prevents Drug-Induced Ototoxicity by Reducing Accumulation of Reactive Oxygen Species in Mouse CochleaYe-Ri Kim0Tae-Jun Kwon1Un-Kyung Kim2In-Kyu Lee3Kyu-Yup Lee4Jeong-In Baek5Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, KoreaLaboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41566, KoreaDepartment of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Internal Medicine, Research Institute of Aging and Metabolism, School of Medicine, Kyungpook National University, Daegu 41566, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University, Daegu 41566, KoreaDepartment of Aroma-Applied Industry, College of Herbal Bio-Industry, Daegu Haany University, Gyeongsan 38610, KoreaDrug-induced hearing loss is a major type of acquired sensorineural hearing loss. Cisplatin and aminoglycoside antibiotics have been known to cause ototoxicity, and excessive accumulation of intracellular reactive oxygen species (ROS) are suggested as the common major pathology of cisplatin- and aminoglycoside antibiotics-induced ototoxicity. Fursultiamine, also called thiamine tetrahydrofurfuryl disulfide, is a thiamine disulfide derivative that may have antioxidant effects. To evaluate whether fursultiamine can prevent cisplatin- and kanamycin-induced ototoxicity, we investigated their preventive potential using mouse cochlear explant culture system. Immunofluorescence staining of mouse cochlear hair cells showed that fursultiamine pretreatment reduced cisplatin- and kanamycin-induced damage to both inner and outer hair cells. Fursultiamine attenuated mitochondrial ROS accumulation as evidenced by MitoSOX Red staining and restored mitochondrial membrane potential in a JC-1 assay. In addition, fursultiamine pretreatment reduced active caspase-3 and TUNEL signals after cisplatin or kanamycin treatment, indicating that fursultiamine decreased apoptotic hair cell death. This study is the first to show a protective effect of fursultiamine against cisplatin- and aminoglycoside antibiotics-induced ototoxicity. Our results suggest that fursultiamine could act as an antioxidant and anti-apoptotic agent against mitochondrial oxidative stress.in cochlear hair cells.https://www.mdpi.com/2076-3921/10/10/1526cisplatinkanamycinototoxicityreactive oxygen speciesfursultiamine |
| spellingShingle | Ye-Ri Kim Tae-Jun Kwon Un-Kyung Kim In-Kyu Lee Kyu-Yup Lee Jeong-In Baek Fursultiamine Prevents Drug-Induced Ototoxicity by Reducing Accumulation of Reactive Oxygen Species in Mouse Cochlea Antioxidants cisplatin kanamycin ototoxicity reactive oxygen species fursultiamine |
| title | Fursultiamine Prevents Drug-Induced Ototoxicity by Reducing Accumulation of Reactive Oxygen Species in Mouse Cochlea |
| title_full | Fursultiamine Prevents Drug-Induced Ototoxicity by Reducing Accumulation of Reactive Oxygen Species in Mouse Cochlea |
| title_fullStr | Fursultiamine Prevents Drug-Induced Ototoxicity by Reducing Accumulation of Reactive Oxygen Species in Mouse Cochlea |
| title_full_unstemmed | Fursultiamine Prevents Drug-Induced Ototoxicity by Reducing Accumulation of Reactive Oxygen Species in Mouse Cochlea |
| title_short | Fursultiamine Prevents Drug-Induced Ototoxicity by Reducing Accumulation of Reactive Oxygen Species in Mouse Cochlea |
| title_sort | fursultiamine prevents drug induced ototoxicity by reducing accumulation of reactive oxygen species in mouse cochlea |
| topic | cisplatin kanamycin ototoxicity reactive oxygen species fursultiamine |
| url | https://www.mdpi.com/2076-3921/10/10/1526 |
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