Prophylactic treatment of asthma by an ozone scavenger in a mouse model

Bioorg Med Chem Lett. 2015 Jan 15;25(2):342-6. doi: 10.1016/j.bmcl.2014.11.035. Epub 2014 Nov 20.

Abstract

Our hypothesis that inflammation in asthma involves production of ozone by white blood cells and that ozone could be an inflammatory mediator suggests that scavengers of reactive oxygen species (ROS), for example, electron-rich olefins, could serve for prophylactic treatment of asthma. Olefins could provide chemical protection against either exogenous or endogenous ozone and other ROS. BALB/c mice pretreated by inhalation of d-limonene before an ovalbumin challenge exhibited significant attenuation of the allergic asthma symptoms. Diminution of the inflammatory process was evident by reduced levels of aldehydes, reduced counts of neutrophils in the BAL fluid and by histological tests. A surprising systemic effect was observed by decreased levels of aldehydes in the spleen, suggesting that the examination of tissues and organs that are remote from the inflammation foci could provide valuable information on the distribution of the oxidative stress and may serve as guide for targeted treatment.

Keywords: Aldehyde biomarkers; Asthma; Respiratory inflammation; Systemic oxidative stress; d-Limonene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aldehydes / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Asthma / chemically induced
  • Asthma / drug therapy*
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Cyclohexenes / administration & dosage
  • Cyclohexenes / pharmacology*
  • Disease Models, Animal
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Limonene
  • Lung / drug effects
  • Lung / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Molecular Structure
  • Ovalbumin / toxicity
  • Oxidative Stress / drug effects
  • Ozone / toxicity*
  • Reactive Oxygen Species / metabolism*
  • Spleen / drug effects
  • Spleen / metabolism
  • Structure-Activity Relationship
  • Terpenes / administration & dosage
  • Terpenes / pharmacology*

Substances

  • Aldehydes
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclohexenes
  • Reactive Oxygen Species
  • Terpenes
  • Ozone
  • Ovalbumin
  • Limonene