Distribution Analysis via Mass Spectrometry Imaging of Ephedrine in the Lungs of Rats Orally Administered the Japanese Kampo Medicine Maoto

Mutoh, T.; Matsushita, Shoko; Oyama, Yoshiyuki; Suda, Takafumi; Watanabe, Junko; Kase, Yoshio; Setou, Mitsutoshi

doi:10.1038/srep44098

Cited by 20 publications

(7 citation statements)

References 27 publications

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“…The mass spectrum signal intensity at each point in the IMS analysis in the selected region of the GCL was detected automatically after a region of interest (ROI) was set with MS solution imaging software. The signal intensity in the ROI was measured with a slight modification of a method reported in previous work 66 . In total, an 18-point area in the controls and a 26-point area for NC day 2 were used to measure L-acetylcarnitine, a 143-point area was used for the controls, and a 120-point area was used for NC day 2 to measure PC (38:7) in two mouse retinas.…”

Section: Methodsmentioning

confidence: 99%

Metabolomic changes in the mouse retina after optic nerve injury

Sato

Saigusa

Saito

et al. 2018

Sci Rep

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In glaucoma, although axonal injury drives retinal ganglion cell (RGC) death, little is known about the underlying pathomechanisms. To provide new mechanistic insights and identify new biomarkers, we combined latest non-targeting metabolomics analyses to profile altered metabolites in the mouse whole retina 2, 4, and 7 days after optic nerve crush (NC). Ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry and liquid chromatography Fourier transform mass spectrometry covering wide spectrum of metabolites in combination highlighted 30 metabolites that changed its concentration after NC. The analysis displayed similar changes for purine nucleotide and glutathione as reported previously in another animal model of axonal injury and detected multiple metabolites that increased after the injury. After studying the specificity of the identified metabolites to RGCs in histological sections using imaging mass spectrometry, two metabolites, i.e., L-acetylcarnitine and phosphatidylcholine were increased not only preceding the peak of RGC death in the whole retina but also at the RGC layer (2.3-fold and 1.2-fold, respectively). These phospholipids propose novel mechanisms of RGC death and may serve as early biomarkers of axonal injury. The combinatory metabolomics analyses promise to illuminate pathomechanisms, reveal biomarkers, and allow the discovery of new therapeutic targets of glaucoma.

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Section: Methodsmentioning

confidence: 99%

Metabolomic changes in the mouse retina after optic nerve injury

Sato

Saigusa

Saito

et al. 2018

Sci Rep

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“…The lung has been previously studied by MSI showing xenobiotic distribution in lung (19)(20)(21) or differences induced by inhalation and intratracheal administration. (22) Recently, we reported the use of MSI to evaluate the distribution and retention of salmeterol in lung tissue and the dependence of distribution on administration route (inhalation vs. IV).…”

Section: Introductionmentioning

confidence: 99%

Revealing the Regional Localization and Differential Lung Retention of Inhaled Compounds by Mass Spectrometry Imaging

Hamm

Bäckström

Brülls

et al. 2020

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: For the treatment of respiratory disease, inhaled drug delivery aims to provide direct access to pharmacological target sites while minimizing systemic exposure. Despite this long-held tenet of inhaled therapeutic advantage, there are limited data of regional drug localization in the lungs after inhalation. The aim of this study was to investigate the distribution and retention of different chemotypes typifying available inhaled drugs [slowly dissolving neutral fluticasone propionate (FP) and soluble bases salmeterol and salbutamol] using mass spectrometry imaging (MSI). Methods: Salmeterol, salbutamol, and FP were simultaneously delivered by inhaled nebulization to rats. In the same animals, salmeterol-d 3 , salbutamol-d 3 , and FP-d 3 were delivered by intravenous (IV) injection. Samples of lung tissue were obtained at 2-and 30-minute postdosing, and high-resolution MSI was used to study drug distribution and retention. Results: IV delivery resulted in homogeneous lung distribution for all molecules. In comparison, while inhalation also gave rise to drug presence in the entire lung, there were regional chemotype-dependent areas of higher abundance. At the 30-minute time point, inhaled salmeterol and salbutamol were preferentially retained in bronchiolar tissue, whereas FP was retained in all regions of the lungs. Conclusion: This study clearly demonstrates that inhaled small molecule chemotypes are differentially distributed in lung tissue after inhalation, and that high-resolution MSI can be applied to study these retention patterns.

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“…Carter et al and Brioude et al have successfully used MSI to characterize region‐specific protein or peptide distribution within tissue sections. More recently, Matsumoto et al used MSI to examine the localization and distribution of therapeutic compounds in lung tissue samples; this presents clinicians with the opportunity to investigate therapeutic drug efficacy from an entirely novel perspective.…”

Section: Metabolomic‐driven Discovery Of Biomarkersmentioning

confidence: 99%

Metabolomics in chronic lung diseases

et al. 2019

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Chronic lung diseases represent a significant global burden. Their increasing incidence and complexity render a comprehensive, multidisciplinary and personalized approach to each patient, critically important. Most recently, unique biochemical pathways and disease markers have been identified through large‐scale metabolomic studies. Metabolomics is the study of metabolic pathways and the measurement of unique biomolecules in a living system. Analysing samples from different compartments such as bronchoalveolar lavage fluid (BALF) and plasma has proven useful for the characterization of a number of pathological conditions and offers promise as a clinical tool. For example, several studies using mass spectrometry (MS) have shown alterations in the sphingolipid metabolism of chronic obstructive pulmonary disease (COPD) sufferers. In this article, we present a practical review of the application of metabolomics to the study of chronic lung diseases (CLD): COPD, idiopathic pulmonary fibrosis (IPF) and asthma. The insights, which the analytical strategies employed in metabolomics, have provided to the dissection of the biochemistry of CLD and future clinical biomarkers are explored.

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Distribution Analysis via Mass Spectrometry Imaging of Ephedrine in the Lungs of Rats Orally Administered the Japanese Kampo Medicine Maoto

Cited by 20 publications

References 27 publications

Metabolomic changes in the mouse retina after optic nerve injury

Metabolomic changes in the mouse retina after optic nerve injury

Revealing the Regional Localization and Differential Lung Retention of Inhaled Compounds by Mass Spectrometry Imaging

Metabolomics in chronic lung diseases

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