Banerjee Atrayee, Trueblood Max B, Zhang Xinsheng, Manda Kalyan Reddy, Lobo Prem, Whitefield Philip D, Hagen Donald E, Ercal Nuran
Department of Chemistry, Missouri University of Science and Technology, 400 West 11th Street, Rolla, MO 65409, USA.
Toxicol Lett. 2009 Jun 22;187(3):187-93. doi: 10.1016/j.toxlet.2009.02.022. Epub 2009 Mar 13.
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.
柴油发动机尾气（DEE）的副产物柴油尾气颗粒（DEP）是城市环境中空气传播颗粒物（PM）的主要成分之一。DEP由烟灰、多环芳烃（PAH）、具有氧化还原活性的半醌和过渡金属组成，已知这些物质会产生促氧化和促炎作用，从而导致肺部氧化应激诱导的损伤。本研究的目的是确定新型硫醇抗氧化剂N - 乙酰半胱氨酸酰胺（NACA）是否能保护暴露于DEP的动物免受肺部氧化应激诱导的损伤。为了研究这一点，将预先用NACA（250mg/kg体重）或生理盐水处理的雄性C57BL/6小鼠连续九天暴露于DEP（15mg/m³）或过滤空气（每天1.5 - 3小时）中。在最后一次暴露后24小时处死动物。与仅暴露于DEP的动物相比，暴露于DEP且经NACA处理的动物肺部巨噬细胞数量和黏液栓形成量显著减少。此外，如谷胱甘肽（GSH）、丙二醛（MDA）水平和过氧化氢酶（CAT）活性所示，预先用NACA处理的暴露于DEP的动物氧化应激也明显低于未处理组。此外，如乳酸脱氢酶水平所示，NACA处理的动物中DEP诱导的肺部毒性得到逆转。综上所述，这些数据表明硫醇抗氧化剂NACA可以保护肺部免受DEP诱导的炎症和氧化应激相关损伤。
