β-Cypermethrin and its metabolite 3-phenoxybenzoic acid exhibit immunotoxicity in murine macrophages  

出　　处：《Acta Biochimica et Biophysica Sinica》2017年第12期1083-1091,共9页生物化学与生物物理学报（英文版）

摘　　要：β-Cypermethrin （β-CYP）, one of most important pyrethroids, is widely used to control insects, and has been detected in organisms, including human. Pyrethroids have been shown to pose neurotox- icity, hepatotoxicity, endocrine disruption and reproductity risks, in mammals. However, research in immunotoxicity of pyrethroids, especially their metabolites, is limited. A common metabolite of pyre- throids is 3-phenoxybenzoic acid （3-PBA） in mammals. Thus, in this study, we evaluated the immuno- toxicity of ^-CYP and 3-PBA in mouse macrophages, RAW 264.7 cells. M-I-r assays showed that both i3-CYP and 3-PBA reduced cell viability in a concentration- and time-dependent manner. Flow cytome- try with Annexin-V/PI staining demonstrated that both 13-CYP and 3-PBA induced RAW 264.7 cell apoptosis. Furthermore, our results also 3-PBA-induced cytotoxicity and apoptosis showed that N-acetylcysteine partially blocked β-CYP- and ntrinsic apoptotic pathway was stimulated by both β-CYP and 3-PBA exposure. In addition, we found that β-CYP and 3-PBA inhibited mRNA levels of pro- inflammatory cytokines with or without LPS stimulation. Phagocytosis assay showed that both β-CYP and 3-PBA inhibited phagocytic ability of macrophages. Moreover, it was also found that both β-CYP and 3-PBA increased reactive oxygen species （ROS） levels in RAW 264.7 cells. Accordingly, both β-CYP and 3-PBA were found to regulate the mRNA levels of oxidative stress-related genes in RAW 264.7 cells. Taken together, the results obtained in this study demonstrated that β-CYP and 3-PBA may have immunotoxic effect on macrophages and that elevated ROS may underlie the mechanism. The present study will help to understand the health risks caused by β-CYP and other pyrethroids.β-Cypermethrin （β-CYP）, one of most important pyrethroids, is widely used to control insects, and has been detected in organisms, including human. Pyrethroids have been shown to pose neurotox- icity, hepatotoxicity, endocrine disruption and reproductity risks, in mammals. However, research in immunotoxicity of pyrethroids, especially their metabolites, is limited. A common metabolite of pyre- throids is 3-phenoxybenzoic acid （3-PBA） in mammals. Thus, in this study, we evaluated the immuno- toxicity of ^-CYP and 3-PBA in mouse macrophages, RAW 264.7 cells. M-I-r assays showed that both i3-CYP and 3-PBA reduced cell viability in a concentration- and time-dependent manner. Flow cytome- try with Annexin-V/PI staining demonstrated that both 13-CYP and 3-PBA induced RAW 264.7 cell apoptosis. Furthermore, our results also 3-PBA-induced cytotoxicity and apoptosis showed that N-acetylcysteine partially blocked β-CYP- and ntrinsic apoptotic pathway was stimulated by both β-CYP and 3-PBA exposure. In addition, we found that β-CYP and 3-PBA inhibited mRNA levels of pro- inflammatory cytokines with or without LPS stimulation. Phagocytosis assay showed that both β-CYP and 3-PBA inhibited phagocytic ability of macrophages. Moreover, it was also found that both β-CYP and 3-PBA increased reactive oxygen species （ROS） levels in RAW 264.7 cells. Accordingly, both β-CYP and 3-PBA were found to regulate the mRNA levels of oxidative stress-related genes in RAW 264.7 cells. Taken together, the results obtained in this study demonstrated that β-CYP and 3-PBA may have immunotoxic effect on macrophages and that elevated ROS may underlie the mechanism. The present study will help to understand the health risks caused by β-CYP and other pyrethroids.

关 键 词：β-cypermethrin 3-phenoxybenzoic acid macrophages IMMUNOTOXICITY 

分 类 号：Q2[生物学—细胞生物学]