title: Deoxynivalenol induces apoptosis in chicken splenic lymphocytes via the reactive oxygen species-mediated mitochondrial pathway.
abstract: We investigated the immunotoxicity and cytotoxicity of deoxynivalenol (DON), a mycotoxin, and the mechanism by which it induces apoptosis. Chicken splenic lymphocytes treated with 0-50μg/mL DON for 48h inhibited growth of splenic lymphocytes in a dose-dependent manner, as revealed by the Cell Counting Kit-8 (CCK-8) bioassay. Annexin V-fluorescein isothiocyanate staining indicated that the number of apoptotic and necrotic cells were significantly higher compared with the control (P<0.01). DON treatment induced ROS accumulation, resulting in reduced mitochondrial transmembrane potential, as detected by flow cytometry and 2',7'-dichlorofluorescein acetate and rhodamine 123 labeling, respectively. Enzyme linked immunosorbent assays revealed that the concentrations of p53, Bax, Bak-1, and Caspase-3 increased with increasing DON concentration (P<0.05 or P<0.01), whereas the concentrations of Bcl-2 decreased (P<0.01) compared with the control. These data suggest that DON induces apoptosis in splenic lymphocytes via a ROS-mediated mitochondrial pathway.
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China; Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya'an 625014, China; Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya'an 625014, China. Electronic address: zhihua_ren@126.com.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ren
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China; Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya'an 625014, China; Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya'an 625014, China; School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang 621010, China. Electronic address: wangyachao1688@126.com.
authors.forename: Yachao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China; Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya'an 625014, China; Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya'an 625014, China. Electronic address: 847767028@qq.com.
authors.forename: Huidan
authors.initials: H
authors.lastname: Deng
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China; Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya'an 625014, China; Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya'an 625014, China. Electronic address: 335824070@qq.com.
authors.forename: Youtian
authors.initials: Y
authors.lastname: Deng
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China; Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya'an 625014, China; Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya'an 625014, China. Electronic address: dengjl213@126.com.
authors.forename: Junliang
authors.initials: J
authors.lastname: Deng
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China; Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya'an 625014, China; Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya'an 625014, China. Electronic address: zzcjl@126.com.
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China; Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya'an 625014, China; Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya'an 625014, China. Electronic address: wangyadudu@126.com.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China; Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya'an 625014, China; Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya'an 625014, China. Electronic address: pengxi197313@163.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Peng
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China; Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya'an 625014, China; Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya'an 625014, China. Electronic address: cui580420@sicau.edu.cn.
authors.forename: Hengmin
authors.initials: H
authors.lastname: Cui
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China; Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya'an 625014, China; Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya'an 625014, China. Electronic address: shenliuhong@sohu.com.
authors.forename: Liuhong
authors.initials: L
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D053938:DNA Fragmentation; D006861:Hydrogen Peroxide / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000166:cytology*; D014255:Trichothecenes / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014255:Trichothecenes; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; D053148:Caspase 3; C007262:deoxynivalenol
keywords: Apoptosis; Deoxynivalenol; Mitochondria; Reactive oxygen species