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Differential effects of inhaled R- and S-terbutaline in ovalbumin-induced asthmatic mice.
Int Immunopharmacol 2019; 73:581-589II

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.

Authors+Show Affiliations

School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.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.

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 -