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Differential effects of inhaled R- and S-terbutaline in ovalbumin-induced asthmatic mice.

Abstract

Inhaled terbutaline is commercially available β2-agonist which consists of equivalent amount of R- and S-enantiomer. In this study, we aimed to investigate the effects of single enantiomers of terbutaline and its racemate in an ovalbumin (OVA)-induced mouse model of asthma via. seven days inhalation and the potential mechanisms involved. In a standard experimental asthma model, BALB/c mice were sensitized and challenged with OVA. R-terbutaline (R-ter), S-terbutaline (S-ter) or racemic terbutaline (rac-ter) was given via. nose-only inhalation for one week. Airway responsiveness to methacholine was measured by the plethysmography in conscious mice. Eosinophils counts in blood and bronchoalveolar (BAL) fluid were determined. The OVA-sIgE in plasma and inflammatory cytokines and mediators in BAL fluid or lung tissue were analyzed by ELISA, qRT-PCR or western blotting. Airway inflammation and remodeling were evaluated with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson staining. Drug distribution and deposition after inhalation were determined by LC-MS/MS. Our data showed that R-ter efficiently ameliorated asthma responses, including airway hyperresponsiveness, eosinophils influx and IL-5 in BALF, plasma OVA-sIgE and significantly reduced pulmonary inflammation, peribronchial smooth muscle layer thickness, goblet cell hyperplasia, and deposition of collagen fibers, as well as downregulation of p38 MAPK phosphorylation and NF-κB expression. Racemic mixture exhibited diminished effects while S-ter enhanced airway responsiveness to methacholine and exerted pro-asthmatic effects.

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  • Authors+Show Affiliations

    ,

    School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.

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    School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.

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    School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.

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    Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.

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    Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.

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    Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.

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    Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.

    Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China. Electronic address: went@gdut.edu.cn.

    Source

    International immunopharmacology 73: 2019 Aug pg 581-589

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31234092

    Citation

    Beng, Huimin, et al. "Differential Effects of Inhaled R- and S-terbutaline in Ovalbumin-induced Asthmatic Mice." International Immunopharmacology, vol. 73, 2019, pp. 581-589.
    Beng H, Su H, Wang S, et al. Differential effects of inhaled R- and S-terbutaline in ovalbumin-induced asthmatic mice. Int Immunopharmacol. 2019;73:581-589.
    Beng, H., Su, H., Wang, S., Kuai, Y., Hu, J., Zhang, R., ... Tan, W. (2019). Differential effects of inhaled R- and S-terbutaline in ovalbumin-induced asthmatic mice. International Immunopharmacology, 73, pp. 581-589. doi:10.1016/j.intimp.2019.04.036.
    Beng H, et al. Differential Effects of Inhaled R- and S-terbutaline in Ovalbumin-induced Asthmatic Mice. Int Immunopharmacol. 2019;73:581-589. PubMed PMID: 31234092.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Differential effects of inhaled R- and S-terbutaline in ovalbumin-induced asthmatic mice. AU - Beng,Huimin, AU - Su,Hao, AU - Wang,Shanping, AU - Kuai,Yihe, AU - Hu,Junhua, AU - Zhang,Rui, AU - Liu,Fei, AU - Tan,Wen, Y1 - 2019/06/21/ PY - 2019/01/23/received PY - 2019/04/05/revised PY - 2019/04/17/accepted PY - 2019/6/25/pubmed PY - 2019/6/25/medline PY - 2019/6/25/entrez KW - Airway hyperresponsiveness KW - Asthma KW - Inhalation KW - NF-κB KW - Ovalbumin KW - Terbutaline SP - 581 EP - 589 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 73 N2 - Inhaled terbutaline is commercially available β2-agonist which consists of equivalent amount of R- and S-enantiomer. In this study, we aimed to investigate the effects of single enantiomers of terbutaline and its racemate in an ovalbumin (OVA)-induced mouse model of asthma via. seven days inhalation and the potential mechanisms involved. In a standard experimental asthma model, BALB/c mice were sensitized and challenged with OVA. R-terbutaline (R-ter), S-terbutaline (S-ter) or racemic terbutaline (rac-ter) was given via. nose-only inhalation for one week. Airway responsiveness to methacholine was measured by the plethysmography in conscious mice. Eosinophils counts in blood and bronchoalveolar (BAL) fluid were determined. The OVA-sIgE in plasma and inflammatory cytokines and mediators in BAL fluid or lung tissue were analyzed by ELISA, qRT-PCR or western blotting. Airway inflammation and remodeling were evaluated with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson staining. Drug distribution and deposition after inhalation were determined by LC-MS/MS. Our data showed that R-ter efficiently ameliorated asthma responses, including airway hyperresponsiveness, eosinophils influx and IL-5 in BALF, plasma OVA-sIgE and significantly reduced pulmonary inflammation, peribronchial smooth muscle layer thickness, goblet cell hyperplasia, and deposition of collagen fibers, as well as downregulation of p38 MAPK phosphorylation and NF-κB expression. Racemic mixture exhibited diminished effects while S-ter enhanced airway responsiveness to methacholine and exerted pro-asthmatic effects. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/31234092/Differential_effects_of_inhaled_R-_and_S-terbutaline_in_ovalbumin-induced_asthmatic_mice L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(19)30117-1 DB - PRIME DP - Unbound Medicine ER -