Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary disease

J Pharm Biomed Anal. 2017 Jan 5:132:103-108. doi: 10.1016/j.jpba.2016.09.034. Epub 2016 Sep 26.

Abstract

Serum metabolic profiling can identify the metabolites responsible for discrimination between doxycycline treated and untreated chronic obstructive pulmonary disease (COPD) and explain the possible effect of doxycycline in improving the disease conditions. 1H nuclear magnetic resonance (NMR)-based metabolomics was used to obtain serum metabolic profiles of 60 add-on doxycycline treated COPD patients and 40 patients receiving standard therapy. The acquired data were analyzed using multivariate principal component analysis (PCA), partial least-squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). A clear metabolic differentiation was apparent between the pre and post doxycycline treated group. The distinguishing metabolites lactate and fatty acids were significantly down-regulated and formate, citrate, imidazole and l-arginine upregulated. Lactate and folate are further validated biochemically. Metabolic changes, such as decreased lactate level, inhibited arginase activity and lowered fatty acid level observed in COPD patients in response to add-on doxycycline treatment, reflect the anti-inflammatory action of the drug. Doxycycline as a possible therapeutic option for COPD seems promising.

Keywords: Chronic obstructive pulmonary disease; Doxycycline; Forced expiratory volume; Metabolomics; Nuclear magnetic resonance.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Discriminant Analysis
  • Doxycycline / blood*
  • Doxycycline / therapeutic use
  • Fatty Acids / chemistry
  • Folic Acid / chemistry
  • Humans
  • Lactates / chemistry
  • Least-Squares Analysis
  • Lung / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Metabolome
  • Metabolomics / methods*
  • Middle Aged
  • Multivariate Analysis
  • Principal Component Analysis
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Treatment Outcome

Substances

  • Fatty Acids
  • Lactates
  • Folic Acid
  • Doxycycline