The mechanisms of Paraquat induce lung toxicity

• Main Authors: Yuan-Ting Yang, 楊媛婷
• Other Authors: 洪東榮
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/34030932326681997050

碩士 === 中國醫藥大學 === 藥學系藥物安全碩士班 === 99 === Paraquat (1,1’-dimethyl-4,4’-bipyridium dichloride) is an effective herbicide which is used all over the world. Paraquat induces fatal damage to multiple organs, especially lung. The proposed mechanisms of cytotoxicity of paraquat are redox cycling and intracellular oxidative stress generation. In this study, we investigated the effects and the possible mechanisms of paraquat on the rat lung alveolar epithelial cell line (L2) and mouse lung tissue. In our study, L2 cells were exposed to paraquat (50–900μM) for 24 h. These results showed that cell viability were decreased, malondialdehyde (MDA) and reactive oxygen species (ROS) levels were increased in a dose-dependent manner after paraquat exposure for 24 h. Besides, paraquat treatment increased proteins of BAX, cytosol apoptosis-inducing factor (AIF) and cytosol Endonuclease G (Endo G) expression, and enhanced mitochondrial membrane potential depolarization. Furthermore, mitochondria-related apoptotic signals of mRNAs of BAX, BID and P53 were all increased in L2 cell after exposure to paraquat. In addition, mRNAs levels of endoplasmic reticulum stress (ER stress) related apoptotic signals of ATF4, ATF6, GRP78 and CHOP were also significantly increased. These results suggest that paraquat might induce alveolar epithelial cell death through both mitochondria- and ER stress-related pathways. These observations provide evidence that paraquat is an environmental risk factor for pulmonary injury.