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Roxithromycin reduces the viability of cultured airway smooth muscle cells from a rat model of asthma.

AbstractOBJECTIVES:
The purpose of this study was to investigate the effect of roxithromycin on apoptosis of airway smooth muscle cells (ASMCs) from a rat model of asthma and uncover signaling pathway underlying the cytotoxicity of roxithromycin.
MATERIALS AND METHODS:
ASMCs were isolated from a rat model of asthma and treated with or without roxithromycin for 48 h before parameter detection. Cell viability was assessed by WST-8 assay and flow cytometry after Annexin V/PI double staining. Changes in the mitochondrial membrane potential (ΔΨm) were measured by flow cytometry using JC-1. Cytochrome C (Cyt c), cleaved Caspase-9/3 and P27 were evaluated by Western Blot.
RESULTS:
Incubation with roxithromycin reduced ASMCs proliferation and enhanced apoptosis in a dose-dependent manner. Flow cytometry revealed a loss of ΔΨm and Western Blot displayed Caspase-9/3 activation as well as Cyt c release from mitochondria to the the cytosol after the treatment of roxithromycin. In addition, P27 were more strongly expressed in AMSCs treated with roxithromycin compared with the control group.
CONCLUSIONS:
Roxithromycin induced apoptosis of ASMCs derived from a rat model of asthma in a dose-dependent manner via a caspase-3- and caspase-9-dependent mitochondrial pathway, involving the up-regulation of P27.
AuthorsY-R Dai, H-Y Wu, L-Q Wu, H Xu, J Yin, S-S Yan, W-X Zeng
JournalEuropean review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 18 Issue 23 Pg. 3564-72 ( 2014) ISSN: 2284-0729 [Electronic] Italy
PMID25535124 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Roxithromycin
Topics
  • Animals
  • Apoptosis (drug effects, physiology)
  • Asthma (drug therapy, metabolism, pathology)
  • Cell Proliferation (drug effects, physiology)
  • Cell Survival (drug effects, physiology)
  • Cells, Cultured
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Myocytes, Smooth Muscle (drug effects, metabolism, pathology)
  • Rats
  • Rats, Sprague-Dawley
  • Roxithromycin (therapeutic use, toxicity)

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