Addition of exogenous NAD+ prevents mefloquine-induced neuroaxonal and hair cell degeneration through reduction of caspase-3-mediated apoptosis in cochlear organotypic cultures.

Ding D, Qi W, Yu D, Jiang H, Han C, Kim MJ, Katsuno K, Hsieh YH, Miyakawa T, Salvi R, Tanokura M, Someya S

PloS one6 Nov 2013Cited by 42 (Europe PMC)

PMID24223197PMCIDPMC3819247DOI10.1371/journal.pone.0079817PepBankPUB-24223197

Summary

BackgroundMefloquine is widely used for the treatment of malaria. However, this drug is known to induce neurological side effects including depression, anxiety, balance disorder, and sensorineural hearing loss. Yet, there is currently no treatment for these side effects.Principal findingsIn this study, we show that the coenzyme NAD(+), known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae. Mefloquine alone destroyed hair cells and nerve fiber axons in rat cochlear organotypics cultures in a dose-dependent manner, while treatment with NAD(+) protected axons and hair cells from mefloquine-induced degeneration. Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3. Treatment with NAD(+) reduced the levels of these oxidative stress and apoptosis markers.Conclusions/significanceTaken together, our findings suggest that that mefloquine disrupts the cellular redox environment and induces oxidative stress in cochlear hair cells and nerve fibers leading to caspases-3-mediated apoptosis of these structures. Exogenous NAD(+) suppresses mefloquine-induced oxidative stress and prevents the degeneration of cochlear axons and sensory hair cells caused by mefloquine treatment.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. No result from this study comes from people.

01LabEx vivo tissueEfficacy outcome
In cultured rat cochleae, NAD protected axons against mefloquine-induced degeneration compared with mefloquine alone.
In plain wordsIn lab tests with rat cochleae, NAD protected axons from degeneration compared with mefloquine alone.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseCochlear axon degeneration
Study
ratn: not reported in source
Cochlear organotypic cultures exposed to mefloquine
Comparator
Mefloquine alone
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Mefloquine alone destroyed hair cells and nerve fiber axons in rat cochlear organotypics cultures in a dose-dependent manner, while treatment with NAD(+) protected axons and hair cells from mefloquine-induced degeneration.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, we show that the coenzyme NAD(+), known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae.
Show in the study text Report a problemFND-2422319701
02LabEx vivo tissueEfficacy outcome
In cultured rat cochleae, NAD protected sensory hair cells against degeneration compared with mefloquine alone.
In plain wordsIn lab tests with rat cochleae, NAD protected sensory hair cells from degeneration compared with mefloquine alone.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseSensory hair cell degeneration
Study
ratn: not reported in source
Cochlear organotypic cultures exposed to mefloquine
Comparator
Mefloquine alone
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Mefloquine alone destroyed hair cells and nerve fiber axons in rat cochlear organotypics cultures in a dose-dependent manner, while treatment with NAD(+) protected axons and hair cells from mefloquine-induced degeneration.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, we show that the coenzyme NAD(+), known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae.
Show in the study text Report a problemFND-2422319702
03LabEx vivo tissueMechanism
In cultured rat cochleae, NAD reduced superoxide levels induced by mefloquine.
In plain wordsIn lab tests with rat cochleae, NAD reduced superoxide levels induced by mefloquine.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseSuperoxide levels
Study
ratn: not reported in source
Cochlear organotypic cultures exposed to mefloquine
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Treatment with NAD(+) reduced the levels of these oxidative stress and apoptosis markers.
2 context sentences(design, population, supporting numbers)
Summary · context
Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3.
Summary · context
In this study, we show that the coenzyme NAD(+), known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae.
Show in the study text Report a problemFND-2422319703
04LabEx vivo tissueMechanism
In cultured rat cochleae, NAD reduced protein carbonyl levels induced by mefloquine.
In plain wordsIn lab tests with rat cochleae, NAD reduced protein carbonyl levels induced by mefloquine.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseProtein carbonyl levels
Study
ratn: not reported in source
Cochlear organotypic cultures exposed to mefloquine
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Treatment with NAD(+) reduced the levels of these oxidative stress and apoptosis markers.
2 context sentences(design, population, supporting numbers)
Summary · context
Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3.
Summary · context
In this study, we show that the coenzyme NAD(+), known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae.
Show in the study text Report a problemFND-2422319704
05LabEx vivo tissueMechanism
In cultured rat cochleae, NAD reduced TUNEL-positive nuclei induced by mefloquine.
In plain wordsIn lab tests with rat cochleae, NAD reduced TUNEL-positive nuclei induced by mefloquine.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseTUNEL-positive nuclei
Study
ratn: not reported in source
Cochlear organotypic cultures exposed to mefloquine
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Treatment with NAD(+) reduced the levels of these oxidative stress and apoptosis markers.
2 context sentences(design, population, supporting numbers)
Summary · context
Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3.
Summary · context
In this study, we show that the coenzyme NAD(+), known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae.
Show in the study text Report a problemFND-2422319705
06LabEx vivo tissueMechanism
In cultured rat cochleae, NAD reduced caspases-3 levels induced by mefloquine.
In plain wordsIn lab tests with rat cochleae, NAD reduced caspases-3 levels induced by mefloquine.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseCaspases-3 levels
Study
ratn: not reported in source
Cochlear organotypic cultures exposed to mefloquine
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Treatment with NAD(+) reduced the levels of these oxidative stress and apoptosis markers.
2 context sentences(design, population, supporting numbers)
Summary · context
Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3.
Summary · context
In this study, we show that the coenzyme NAD(+), known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae.
Show in the study text Report a problemFND-2422319706

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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