Metabolomic profiling in inner ear fluid by gas chromatography/mass spectrometry in guinea pig cochlea

Fujita, Takeshi; Yamashita, Daisuke; Irino, Yasuhiro; Kitamoto, Junko; Fukuda, Yujiro; Inokuchi, Go; Hasegawa, Shingo; Otsuki, Naoki; Yoshida, Masaru; Nibu, Ken‐ichi

doi:10.1016/j.neulet.2015.09.001

Cited by 24 publications

(37 citation statements)

References 26 publications

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“…Some attention has been directed at characterizing the small metabolites of perilymph using mainly HPLC with fluorescence detection (Drescher, Medina and Drescher 1981; Medina and Drescher 1981; Scheibe and Haupt 1985; Bobbin and Fallon 1992). The qualitative composition of perilymph, in terms of proteins and small metabolites, is comparable to that of both CSF and blood plasma, whereas the relative concentrations differ widely between the three fluids (Scheibe and Haupt 1985; Leary Swan et al 2009; Fujita et al 2015). Notably, Fujita et al (2015) used a GCMS-based metabolomics protocol to study the effect of noise on the metabolome of the inner ear fluid of guinea pigs.…”

Section: Introductionmentioning

confidence: 99%

“…The qualitative composition of perilymph, in terms of proteins and small metabolites, is comparable to that of both CSF and blood plasma, whereas the relative concentrations differ widely between the three fluids (Scheibe and Haupt 1985; Leary Swan et al 2009; Fujita et al 2015). Notably, Fujita et al (2015) used a GCMS-based metabolomics protocol to study the effect of noise on the metabolome of the inner ear fluid of guinea pigs. They found ten metabolites that were significantly altered in concentration in inner ear fluid, whereas no altered metabolite concentrations were found in blood.…”

Section: Introductionmentioning

confidence: 99%

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An LCMS-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed Guinea pigs

et al. 2019

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Introduction Noise-induced hearing loss (NIHL) is an increasing problem in society and accounts for a third of all cases of acquired hearing loss. NIHL is caused by formation of reactive oxygen species (ROS) in the cochlea causing oxidative stress. Hydrogen gas (H2) can alleviate the damage caused by oxidative stress and can be easily administered through inhalation. Objectives To present a protocol for untargeted metabolomics of guinea pig perilymph and investigate the effect of H2 administration on the perilymph metabolome of noise exposed guinea pigs. Methods The left ear of guinea pigs were exposed to hazardous impulse noise only (Noise, n = 10), noise and H2 (Noise + H2, n = 10), only H2 (H2, n = 4), or untreated (Control, n = 2). Scala tympani perilymph was sampled from the cochlea of both ears. The polar component of the perilymph metabolome was analyzed using a HILIC-UHPLC-Q-TOF–MS-based untargeted metabolomics protocol. Multivariate data analysis (MVDA) was performed separately for the exposed- and unexposed ear. Results MVDA allowed separation of groups Noise and Noise + H2 in both the exposed and unexposed ear and yielded 15 metabolites with differentiating relative abundances. Seven were found in both exposed and unexposed ear data and included two osmoprotectants. Eight metabolites were unique to the unexposed ear and included a number of short-chain acylcarnitines. Conclusions A HILIC-UHPLC-Q-TOF–MS-based protocol for untargeted metabolomics of perilymph is presented and shown to be fit-for-purpose. We found a clear difference in the perilymph metabolome of noise exposed guinea pigs with and without H2 treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An LCMS-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed Guinea pigs

et al. 2019

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“…Metabolomics is the study of systematic changes in small molecule metabolites present in biological samples and is an effective tool for understanding disease phenotypes (Fujita et al, 2015). There have been a number of recent metabolomics studies of pain.…”

Section: Introductionmentioning

confidence: 99%

Urinary metabolomics of complete Freund's adjuvant‐induced hyperalgesia in rats

Liu

Chen

et al. 2017

Biomedical Chromatography

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The aim of this study was to demonstrate the differences of metabolomics changes in a hyperalgesia model and find potent biomarkers of hyperalgesia. Seven rats were placed in metabolic cages. An emulsion containing 500 μg of Complete Freund's adjuvant (CFA) was used to induce hyperalgesia. Urine samples were collected prior to the injection of CFA and on post-injection days 1, 3 and 7. Ultraperformance liquid chromatography, coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), was used for a quantitative analysis of urinary metabolic changes in the CFA-induced hyperalgesia model. Differences between the metabolic profiles of the rats in the four groups were analyzed using partial least squares discriminant analysis. Thirty-four potential urine metabolite biomarkers were identified, which changed in a trend similar to the pain threshold. These potential biomarkers were involved in 11 metabolic pathways, as follows: alanine, aspartate, and glutamate metabolism; ascorbate and aldarate metabolism; glycerolipid metabolism; glycerophospholipid metabolism; histidine metabolism; phenylalanine metabolism; sphingolipid metabolism; tryptophan metabolism; tyrosine metabolism; valine, leucine and isoleucine biosynthesis; and vitamin B6 metabolism. These results may improve our understanding of hyperalgesia and provide a basis for the clinical diagnosis of hyperalgesia.

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“…Fujita et al . 15 measured the effects of a strong noise exposure (126 dB SPL) on the metabolome of guinea pig inner ear fluids while Mavel et al . 16 analyzed the perilymph of humans who were undergoing cochlear implantation.…”

Section: Discussionmentioning

confidence: 99%

“…Our results on the effects of noise differ significantly from those of Fujita et al . 15 . Specifically, we measured the abundance of 220 metabolites, while their approach allowed for the detection of only 77.…”

Section: Discussionmentioning

confidence: 99%

Auditory metabolomics, an approach to identify acute molecular effects of noise trauma

Lee

Wan

et al. 2019

Sci Rep

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Animal-based studies have provided important insights into the structural and functional consequences of noise exposure on the cochlea. Yet, less is known about the molecular mechanisms by which noise induces cochlear damage, particularly at relatively low exposure levels. While there is ample evidence that noise exposure leads to changes in inner ear metabolism, the specific effects of noise exposure on the cochlear metabolome are poorly understood. In this study we applied liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based metabolomics to analyze the effects of noise on the mouse inner ear. Mice were exposed to noise that induces temporary threshold shifts, synaptopathy and permanent hidden hearing loss. Inner ears were harvested immediately after exposure and analyzed by targeted metabolomics for the relative abundance of 220 metabolites across the major metabolic pathways in central carbon metabolism. We identified 40 metabolites differentially affected by noise. Our approach detected novel noise-modulated metabolites and pathways, as well as some already linked to noise exposure or cochlear function such as neurotransmission and oxidative stress. Furthermore, it showed that metabolic effects of noise on the inner ear depend on the intensity and duration of exposure. Collectively, our results illustrate that metabolomics provides a powerful approach for the characterization of inner ear metabolites affected by auditory trauma. This type of information could lead to the identification of drug targets and novel therapies for noise-induced hearing loss.

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Metabolomic profiling in inner ear fluid by gas chromatography/mass spectrometry in guinea pig cochlea

Cited by 24 publications

References 26 publications

An LCMS-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed Guinea pigs

An LCMS-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed Guinea pigs

Urinary metabolomics of complete Freund's adjuvant‐induced hyperalgesia in rats

Auditory metabolomics, an approach to identify acute molecular effects of noise trauma

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