Platinum nanoparticle antioxidants inhibit pulmonary inflammation in mice exposed to cigarette smoke

Pulm Pharmacol Ther. 2009 Aug;22(4):340-9. doi: 10.1016/j.pupt.2008.12.015. Epub 2008 Dec 31.

Abstract

Recent evidence implicates increased oxidative stress as an important mechanism of the pulmonary inflammation that occurs in cigarette smokers. Since cigarette smoke (CS) contains and generates a large amount of reactive oxygen species (ROS) that elicit pulmonary inflammation, antioxidants may become effective therapeutic agents for CS-related inflammatory lung diseases, such as chronic obstructive pulmonary disease. Platinum nanoparticles stabilized with polyacrylate to form a stable colloid solution (PAA-Pt) are a new class of antioxidants that has been shown to efficiently quench ROS. In the present study we investigated the therapeutic effects of PAA-Pt on pulmonary inflammation in smoking mice. PAA-Pt or saline was administered intranasally to DBA/2 mice, which were then exposed to CS or control air daily for 3 days. Mice were sacrificed 4h after their final exposure to CS or control air. CS exposure caused depletion of antioxidant capacity, NFkappaB activation, and neutrophilic inflammation in the lungs of mice, and intranasal administration of PAA-Pt prior to CS exposure was found to inhibit these changes. Intranasal administration of PAA-Pt alone did not elicit pulmonary inflammation or toxicity. In in vitro experiments, treatment of alveolar-type-II-like A549 cells with PAA-Pt inhibited cell death after exposure to a CS extract. These results suggest that platinum nanoparticles act as antioxidants that inhibit pulmonary inflammation induced by acute cigarette smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemotaxis, Leukocyte / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Hydrogen Peroxide / metabolism
  • In Situ Nick-End Labeling
  • Leukocyte Elastase / metabolism
  • Male
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred DBA
  • NF-kappa B / metabolism
  • Nanoparticles
  • Oxidative Stress / drug effects
  • Platinum / administration & dosage
  • Platinum / pharmacokinetics
  • Platinum / pharmacology*
  • Pneumonia / chemically induced*
  • Pneumonia / pathology*
  • Reactive Oxygen Species
  • Smoke*
  • Tobacco / chemistry*

Substances

  • Antioxidants
  • NF-kappa B
  • Reactive Oxygen Species
  • Smoke
  • Platinum
  • Hydrogen Peroxide
  • Leukocyte Elastase
  • Matrix Metalloproteinases