Dextromethorphan Attenuates Nanoparticles-Induced Inflammation and Oxidative Stress in Alveolar Epithelial Cells and Macrophages

• Main Authors: Wen-Jhe Wong, 翁文哲
• Other Authors: Yi-Ching Lo
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/34362848096674062934

碩士 === 高雄醫學大學 === 藥理學研究所 === 100 === Nanoparticles cause pulmonary toxicity mainly through inflammation. Carbon black nanoparticles (CBNPs) have been widely used in various commercial products and found in many different environmental exposures. Here, we examined the cytotoxic mechanisms of CBNPs in alveolar epithelial cells (A549) and macrophages (RAW264.7) and evaluated the potential benefits of dextromethorphan (DM), an anti-tussive agent, on nanoparticles-induced toxicity. Results indicated CBNPs significantly increased the inflammatory markers (COX2/PGE2 and iNOS/NO) and oxidative stress markers (NADPH oxidase and ROS) in A549 and RAW264.7 cells and CBNPs significantly increased PKC-?? activation in A549 cells. Furthermore, with various pharmacological inhibitor treatments, we proved CBNPs-induced cytotoxic effects through PKC-??/NOX/COX-2, iNOS pathway in A549 cells and NOX/COX-2, iNOS pathway in RAW264.7 cells. The cytotoxic effects were significantly inhibited by DM treatment. The present results indicated that CBNPs enhance cellular inflammatory response and oxidative stress, which were attenuated by DM treatment.