Related Experiment Video

Updated: Jun 29, 2025

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
09:52

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity

Published on: March 16, 2018

9.4K

Ivacaftor attenuates gentamicin-induced ototoxicity through the CFTR-Nrf2-HO1/NQO1 pathway

Rui Hu1,2, Fan Wu2,3,4, Yi-Qing Zheng1,2,3

  • 1Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, Shanwei, People's Republic of China.

Redox Report : Communications in Free Radical Research
|April 2, 2024
PubMed
Abstract

Insights

Ivacaftor, a CFTR activator, protects against gentamicin-induced ototoxicity by reducing oxidative stress and apoptosis. This suggests potential for treating aminoglycoside-induced hearing loss.

Area of Science:

  • Ototoxicity research
  • Drug discovery
  • Cellular biology

Background:

  • Gentamicin is a common ototoxic drug causing hearing loss.
  • Oxidative stress is a key factor in gentamicin-induced hair cell death.
  • No effective treatments currently exist for this hearing loss.

Purpose of the Study:

  • To evaluate ivacaftor's effect on gentamicin-induced ototoxicity.
  • To elucidate the mechanism of ivacaftor's protective action.

Main Methods:

  • In vitro cochlear explant model.
  • Myosin 7a staining for hair cell count.
  • TUNEL assay for apoptosis.
  • DCFH-DA probes for reactive oxygen species (ROS).
  • Western blot for Nrf2 pathway proteins.

Main Results:

  • Gentamicin induced ROS accumulation and apoptosis in hair cells.
  • Ivacaftor pretreatment alleviated gentamicin's ototoxic effects.
  • Ivacaftor increased Nrf2, HO1, and NQO1 protein expression.
  • The Nrf2 inhibitor ML385 abolished ivacaftor's protective effect.

Conclusions:

  • The CFTR-Nrf2-HO1/NQO1 pathway is protective against gentamicin ototoxicity.
  • Ivacaftor shows potential for treating aminoglycoside-induced hearing loss.
Keywords:
Gentamicin, ototoxicity, sensory hair cells, CFTR, ivacaftor, Nrf2, oxidative stress, reactive oxygen species

More Related Videos

Dissection of Adult Mouse Utricle and Adenovirus-mediated Supporting-cell Infection11:13

Dissection of Adult Mouse Utricle and Adenovirus-mediated Supporting-cell Infection

Published on: March 28, 2012

23.8K
Nasal Potential Difference to Quantify Trans-epithelial Ion Transport in Mice08:55

Nasal Potential Difference to Quantify Trans-epithelial Ion Transport in Mice

Published on: July 4, 2018

7.8K

Related Concept Videos

Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.2K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.5K
Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
180
Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
1.7K