N-acetylcysteineamide (NACA) prevents inflammation and oxidative stress in animals exposed to diesel engine exhaust.
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 (250mg/kg body weight) or saline, were exposed to DEPs (15mg/m(3)) or filtered air (1.5-3h/day) for nine consecutive days. The animals were sacrificed 24h 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.
Banerjee
Atrayee
A
Department of Chemistry, Missouri University of Science and Technology, 400 West 11th Street, Rolla, MO 65409, USA.
Trueblood
Max B
MB
Zhang
Xinsheng
X
Manda
Kalyan Reddy
KR
Lobo
Prem
P
Whitefield
Philip D
PD
Hagen
Donald E
DE
Ercal
Nuran
N
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006651:Histocytochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D001335:Vehicle Emissions / Q000633:toxicity*
D000975:Antioxidants; D001335:Vehicle Emissions; C487056:N-Acetylcysteinamide; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine