Dataset Information

Pre-treatment With Fasudil Prevents Neomycin-Induced Hair Cell Damage by Reducing the Accumulation of Reactive Oxygen Species.

ABSTRACT: Ototoxic drug-induced hair cell (HC) damage is one of the main causes of sensorineural hearing loss, which is one of the most common sensory disorders in humans. Aminoglycoside antibiotics are common ototoxic drugs, and these can cause the accumulation of intracellular oxygen free radicals and lead to apoptosis in HCs. Fasudil is a Rho kinase inhibitor and vasodilator that has been widely used in the clinic and has been shown to have neuroprotective effects. However, the possible application of fasudil in protecting against aminoglycoside-induced HC loss and hearing loss has not been investigated. In this study, we investigated the ability of fasudil to protect against neomycin-induced HC loss both in vitro and in vivo. We found that fasudil significantly reduced the HC loss in cochlear whole-organ explant cultures and reduced the cell death of auditory HEI-OC1 cells after neomycin exposure in vitro. Moreover, we found that fasudil significantly prevented the HC loss and hearing loss of mice in the in vivo neomycin damage model. Furthermore, we found that fasudil could significantly inhibit the Rho signaling pathway in the auditory HEI-OC1 cells after neomycin exposure, thus further reducing the neomycin-induced accumulation of reactive oxygen species and subsequent apoptosis in HEI-OC1 cells. This study suggests that fasudil might contribute to the increased viability of HCs after neomycin exposure by inhibition of the Rho signaling pathway and suggests a new therapeutic target for the prevention of aminoglycoside-induced HC loss and hearing loss.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6851027 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pre-treatment With Fasudil Prevents Neomycin-Induced Hair Cell Damage by Reducing the Accumulation of Reactive Oxygen Species.

Zhang Yanqiu Y Li Wei W He Zuhong Z Wang Yunfeng Y Shao Buwei B Cheng Cheng C Zhang Shasha S Tang Mingliang M Qian Xiaoyun X Kong Weijia W Wang Hui H Chai Renjie R Gao Xia X

Frontiers in molecular neuroscience 20191106

Ototoxic drug-induced hair cell (HC) damage is one of the main causes of sensorineural hearing loss, which is one of the most common sensory disorders in humans. Aminoglycoside antibiotics are common ototoxic drugs, and these can cause the accumulation of intracellular oxygen free radicals and lead to apoptosis in HCs. Fasudil is a Rho kinase inhibitor and vasodilator that has been widely used in the clinic and has been shown to have neuroprotective effects. However, the possible application of ...[more]

PMID: 31780893

Similar Datasets

Project description:BACKGROUND: Biofuels offer a viable alternative to petroleum-based fuel. However, current methods are not sufficient and the technology required in order to use lignocellulosic biomass as a fermentation substrate faces several challenges. One challenge is the need for a robust fermentative microorganism that can tolerate the inhibitors present during lignocellulosic fermentation. These inhibitors include the furan aldehyde, furfural, which is released as a byproduct of pentose dehydration during the weak acid pretreatment of lignocellulose. In order to survive in the presence of furfural, yeast cells need not only to reduce furfural to the less toxic furan methanol, but also to protect themselves and repair any damage caused by the furfural. Since furfural tolerance in yeast requires a functional pentose phosphate pathway (PPP), and the PPP is associated with reactive oxygen species (ROS) tolerance, we decided to investigate whether or not furfural induces ROS and its related cellular damage in yeast. RESULTS: We demonstrated that furfural induces the accumulation of ROS in Saccharomyces cerevisiae. In addition, furfural was shown to cause cellular damage that is consistent with ROS accumulation in cells which includes damage to mitochondria and vacuole membranes, the actin cytoskeleton and nuclear chromatin. The furfural-induced damage is less severe when yeast are grown in a furfural concentration (25 mM) that allows for eventual growth after an extended lag compared to a concentration of furfural (50 mM) that prevents growth. CONCLUSION: These data suggest that when yeast cells encounter the inhibitor furfural, they not only need to reduce furfural into furan methanol but also to protect themselves from the cellular effects of furfural and repair any damage caused. The reduced cellular damage seen at 25 mM furfural compared to 50 mM furfural may be linked to the observation that at 25 mM furfural yeast were able to exit the furfural-induced lag phase and resume growth. Understanding the cellular effects of furfural will help direct future strain development to engineer strains capable of tolerating or remediating ROS and the effects of ROS.

Dataset Information

Pre-treatment With Fasudil Prevents Neomycin-Induced Hair Cell Damage by Reducing the Accumulation of Reactive Oxygen Species.

Publications

Pre-treatment With Fasudil Prevents Neomycin-Induced Hair Cell Damage by Reducing the Accumulation of Reactive Oxygen Species.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets