Some Ototoxic Drugs Destroy Cochlear Support Cells Before Damaging Sensory Hair Cells
A wide variety of ototoxic drugs are capable of damaging the sensory hair cells in the mammalian cochlea resulting in permanent hearing loss. However, the toxic properties of these drugs suggest that some could potentially damage cochlear support cells as well. To test the hypothesis, we treated postnatal day three rat cochlear cultures with toxic doses of gentamicin, cisplatin, mefloquine, and cadmium. Gentamicin primarily destroyed the hair cells and disrupted the intercellular connection with the surrounding support cells. Gentamicin-induced hair cell death was initiated through the caspase-9 intrinsic apoptotic pathway followed by activation of downstream executioner caspase-3. In contrast, cisplatin, mefloquine, and cadmium initially damaged the support cells and only later damaged the hair cells. Support cell death was initiated through the caspase-8 extrinsic apoptotic pathway followed later by downstream activation of caspase-3. Cisplatin, mefloquine, and cadmium significantly reduced the expression of actin and laminin, in the extracellular matrix, leading to significant disarray of the sensory epithelium.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
|---|---|
| Enthalten in: |
Neurotoxicity research - 37(2020), 3 vom: 29. März, Seite 743-752 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ding, Dalian [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
00BH33GNGH |
|---|
| Anmerkungen: |
Date Completed 04.12.2020 Date Revised 25.10.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s12640-020-00170-8 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM305930273 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM305930273 | ||
| 003 | DE-627 | ||
| 005 | 20231225122236.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s12640-020-00170-8 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1019.xml |
| 035 | |a (DE-627)NLM305930273 | ||
| 035 | |a (NLM)31997155 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ding, Dalian |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Some Ototoxic Drugs Destroy Cochlear Support Cells Before Damaging Sensory Hair Cells |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.12.2020 | ||
| 500 | |a Date Revised 25.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A wide variety of ototoxic drugs are capable of damaging the sensory hair cells in the mammalian cochlea resulting in permanent hearing loss. However, the toxic properties of these drugs suggest that some could potentially damage cochlear support cells as well. To test the hypothesis, we treated postnatal day three rat cochlear cultures with toxic doses of gentamicin, cisplatin, mefloquine, and cadmium. Gentamicin primarily destroyed the hair cells and disrupted the intercellular connection with the surrounding support cells. Gentamicin-induced hair cell death was initiated through the caspase-9 intrinsic apoptotic pathway followed by activation of downstream executioner caspase-3. In contrast, cisplatin, mefloquine, and cadmium initially damaged the support cells and only later damaged the hair cells. Support cell death was initiated through the caspase-8 extrinsic apoptotic pathway followed later by downstream activation of caspase-3. Cisplatin, mefloquine, and cadmium significantly reduced the expression of actin and laminin, in the extracellular matrix, leading to significant disarray of the sensory epithelium | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Caspase | |
| 650 | 4 | |a Cochlea | |
| 650 | 4 | |a Hair cells | |
| 650 | 4 | |a Necrosis | |
| 650 | 4 | |a Ototoxicity | |
| 650 | 4 | |a Support cells | |
| 650 | 7 | |a Gentamicins |2 NLM | |
| 650 | 7 | |a Cadmium |2 NLM | |
| 650 | 7 | |a 00BH33GNGH |2 NLM | |
| 650 | 7 | |a Caspases |2 NLM | |
| 650 | 7 | |a EC 3.4.22.- |2 NLM | |
| 650 | 7 | |a Cisplatin |2 NLM | |
| 650 | 7 | |a Q20Q21Q62J |2 NLM | |
| 650 | 7 | |a Mefloquine |2 NLM | |
| 650 | 7 | |a TML814419R |2 NLM | |
| 700 | 1 | |a Zhang, Jianhui |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Haiyan |e verfasserin |4 aut | |
| 700 | 1 | |a Xuan, Weijun |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Weidong |e verfasserin |4 aut | |
| 700 | 1 | |a Salvi, Richard |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neurotoxicity research |d 1999 |g 37(2020), 3 vom: 29. März, Seite 743-752 |w (DE-627)NLM124802664 |x 1476-3524 |7 nnns |
| 773 | 1 | 8 | |g volume:37 |g year:2020 |g number:3 |g day:29 |g month:03 |g pages:743-752 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s12640-020-00170-8 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 37 |j 2020 |e 3 |b 29 |c 03 |h 743-752 | ||