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

• Published in: Pulmonary pharmacology & therapeutics Vol. 22; no. 4; pp. 340 - 349
• Main Authors: Onizawa, Shigemitsu, Aoshiba, Kazutetsu, Kajita, Masashi, Miyamoto, Yusei, Nagai, Atsushi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2009
• Subjects: Administration, Intranasal; Animals; Antioxidant; Antioxidants - administration & dosage; Antioxidants - pharmacology; Blotting, Western; Bronchoalveolar Lavage Fluid - cytology; Chemotaxis, Leukocyte - drug effects; Cigarette smoke; Enzyme-Linked Immunosorbent Assay; Hydrogen Peroxide - metabolism; In Situ Nick-End Labeling; Leukocyte Elastase - metabolism; Lung inflammation; Male; Matrix Metalloproteinases - metabolism; Medical Education; Mice; Mice, Inbred DBA; Nanoparticles; Neutrophil; NF-kappa B - metabolism; NFκB; Nicotiana - chemistry; Oxidant; Oxidative Stress - drug effects; Platinum - administration & dosage; Platinum - pharmacokinetics; Platinum - pharmacology; Platinum nanoparticles; Pneumonia - chemically induced; Pneumonia - pathology; Pulmonary/Respiratory; Reactive Oxygen Species; Smoke; Platinum nanoparticles; NFκB; Lung inflammation; Oxidant; Neutrophil; Antioxidant; Cigarette smoke
• ISSN: 1094-5539; 1522-9629
• DOI: 10.1016/j.pupt.2008.12.015

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 4 h after their final exposure to CS or control air. CS exposure caused depletion of antioxidant capacity, NFκB 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.