N-acetylcysteineamide (NACA) Prevents Inflammation and Oxidative Stress in Animals Exposed to Diesel Engine Exhaust

Abstract

Diesel exhaust particles (DEPs), a by-product of diesel engine exhaust (DEE), are one of the major components of air borne particulate matter (PM) in the urban environment. DEPs are composed of soot, polycyclic aromatic hydrocarbons (PAHs), redox active semi-quinones, and transition metals, which are known to produce pro-oxidative and pro-inflammatory effects, thereby leading to oxidative stress-induced damage in the lungs. The objective of this study was to determine if N-acetylcysteineamide (NACA), a novel thiol antioxidant, confers protection to animals exposed to DEPs from oxidative stress-induced damage to the lung. To study this, male C57BL/6 mice, pretreated with either NACA (250 mg/kg body weight) or saline, were exposed to DEPs (15 mg/m3) or filtered air (1.5-3 h/day) for nine consecutive days. The animals were sacrificed 24 h after the last exposure. NACA-treated animals exposed to DEP had significant decreases in the number of macrophages and the amount of mucus plug formation in the lungs, as compared to the DEP-only exposed animals. In addition, DEP-exposed animals, pretreated with NACA, also experienced significantly lower oxidative stress than the untreated group, as indicated by the glutathione (GSH), and malondialdehyde (MDA) levels and catalase (CAT) activity. Further, DEP-induced toxicity in the lungs was reversed in NACA-treated animals, as indicated by the lactate dehydrogenase levels. Taken together, these data suggest that the thiol-antioxidant, NACA, can protect the lungs from DEP-induced inflammation and oxidative stress related damage.

Department(s)

Chemistry

Second Department

Mechanical and Aerospace Engineering

Third Department

Physics

Sponsor(s)

National Institutes of Health (U.S.)

Keywords and Phrases

Antioxidant; Catalase; Cysteine; Glutathione; Lactate Dehydrogenase; Malonaldehyde; N Acetylcysteineamide; Thiol Derivative; Unclassified Drug; Animal Experiment; Animal Model; Animal Tissue; Antiinflammatory Activity; Antioxidant Activity; Controlled Study; Cytotoxicity; Diesel Engine; Enzyme Activity; Exhaust Gas; Lipid Peroxidation; Lung Alveolus Macrophage; Lung Toxicity; Macrophage Migration Inhibition; Male; Mouse; Mucus Secretion; Nonhuman; Oxidative Stress; Pneumonia; Priority Journal; Air - pollution; Antioxidants; Lungs

International Standard Serial Number (ISSN)

0378-4274

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2009 Elsevier, All rights reserved.

Publication Date

01 Jun 2009

Link to Full Text

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