Quantitation of γ<i>‐</i>aminobutyric acid in equine plasma by hydrophilic interaction liquid chromatography with tandem mass spectrometry

Rong, Yi; Zhao, Sarah; Kong, Noel; Zhang, Julia; Loganathan, Devan; Mérette, Sandrine; Morrissey, Barbara

doi:10.1002/jssc.201700245

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…6 A growing body of research describes GABA as an important modulator in cells of the immune system, 13 which is present in nanomolar concentrations in the blood. 14 Our group has demonstrated that nanomolar concentrations of GABA A R allosteric ligands and GABA are sufficient to change the transmembrane current of isolated mouse CD4 + T cells. 7 Oral administration of allosteric GABA A R ligands reduced the number of lung inflammatory cells in ovalbumin-sensitized and challenged asthmatic mice.…”

Section: ■ Introductionmentioning

confidence: 99%

Nebulized MIDD0301 Reduces Airway Hyperresponsiveness in Moderate and Severe Murine Asthma Models

Zahn

Mikulsky²,

Roni

et al. 2020

ACS Pharmacol. Transl. Sci.

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We report the relaxation of methacholine-constricted airways with nebulized MIDD0301, a positive allosteric γ-aminobutyric acid type A receptor (GABA A R) modulator. The therapeutic efficacy of nebulized MIDD0301 in reducing airway resistance was investigated in spontaneous breathing mice using a whole-body plethysmograph and in unconscious mice using a forced oscillation technique. Prophylactic nebulized MIDD0301 reduced subsequent methacholine-induced bronchoconstriction in ovalbumin and house dust mite allergic asthma models and in normal mice. Nebulized MIDD0301 exhibited comparable or better therapeutic potency compared to nebulized albuterol and oral montelukast. Prophylactic nebulized MIDD0301 was also effective in reducing bronchoconstriction, comparable to nebulized albuterol or fluticasone, in a steroid resistant asthma mouse model induced by intratracheal installation of lipopolysaccharide and interferon-gamma. Oral dexamethasone was ineffective in this model. Nebulized MIDD0301 was also effective in reversing bronchospasm when dosed after methacholine challenge comparable to albuterol. Pharmacokinetic studies showed that about 0.06% of nebulized MIDD0301 entered the mouse lung when using a whole body plethysmograph and therapeutic levels were sustained in the lung for at least 25 min. Consistent with previous reports on orally dosed MIDD0301, high doses of nebulized MIDD0301 resulted in minimal brain exposure and thus no observable adverse sensorimotor or respiratory depression effects occurred. In addition, no adverse cardiovascular effects were observed following 100 mg/kg i.p. dosing. These results further demonstrate that charged imidazodiazepine MIDD0301 can selectively target lung GABA A R without adverse motor, cardiovascular, or respiratory effects and inhaled dosing is effective in reducing bronchoconstriction in allergen and infectious lung inflammation.

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Section: ■ Introductionmentioning

confidence: 99%

Nebulized MIDD0301 Reduces Airway Hyperresponsiveness in Moderate and Severe Murine Asthma Models

Zahn

Mikulsky²,

Roni

et al. 2020

ACS Pharmacol. Transl. Sci.

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Advancement in Analytical Strategies for Quantification of Biomarkers with a Special Emphasis on Surrogate Approaches

Mishra,

Rajput,

Jadav

et al. 2022

Critical Reviews in Analytical Chemistry

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Gut Microbiota Combined With Metabolomics Reveals the Repeated Dose Oral Toxicity of β-Cyclodextrin in Mice

Zhang

Feng

et al. 2021

Front. Pharmacol.

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Βeta-cyclodextrin (β-CD) with a hydrophobic cavity enables the formation of inclusion complexes with organic molecules. The formation of host–guest complexes makes the application of β-CD popular in many fields, but their interaction with organisms is poorly understood. In the present study, the effect of β-CD on gut microbiota (16S rRNA gene sequencing), serum metabolites (gas chromatography–mass spectrometry platform), and their correlation (Pearson correlation analysis) was investigated after 14 days repeated oral exposure in mice. β-CD did not significantly affect the α-diversity indexes, including Richness, Chao1, Shannon and Simpson indexes, but disturbed the structure of the gut bacteria according to the result of principal component analysis (PCA). After taxonomic assignment, 1 in 27 phyla, 2 in 48 classes, 3 in 107 orders, 6 in 192 families, and 8 in 332 genera were significantly different between control and β-CD treated groups. The serum metabolites were significantly changed after β-CD treatment according to the result of unsupervized PCA and supervised partial least squares-discriminant analysis (PLS-DA). A total of 112 differential metabolites (89 downregulated and 23 upregulated) were identified based on the VIP >1 from orthogonal PLS-DA and p <0.05 from Student’s t-test. The metabolic pathways, including ABC transporters, pyrimidine metabolism, purine metabolism, glucagon signaling pathway, insulin signaling pathway, and glycolysis/gluconeogenesis, were enriched by KEGG pathway analysis. Our study provides a general observation of gut microbiota, serum metabolites and their correlation after exposure to β-CD in mice, which will be helpful for future research and application of β-CD.

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Quantitation of γ‐aminobutyric acid in equine plasma by hydrophilic interaction liquid chromatography with tandem mass spectrometry

Cited by 3 publications

References 39 publications

Nebulized MIDD0301 Reduces Airway Hyperresponsiveness in Moderate and Severe Murine Asthma Models

Nebulized MIDD0301 Reduces Airway Hyperresponsiveness in Moderate and Severe Murine Asthma Models

Advancement in Analytical Strategies for Quantification of Biomarkers with a Special Emphasis on Surrogate Approaches

Gut Microbiota Combined With Metabolomics Reveals the Repeated Dose Oral Toxicity of β-Cyclodextrin in Mice

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