二氧化硫加剧砷对小鼠肝脏的损伤
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摘要
砷(As)与二氧化硫(SO_2)是两种分布极为广泛的环境污染物,二者皆对肝脏有一定毒性.SO_2排放的增加,使许多受到原生高As地下水影响的居民同时遭遇SO_2污染,因此,本文探讨了SO_2对As暴露致肝脏损伤的影响和机制.以C57BL/6小鼠为试验模型,设置对照组、As处理组、SO_2处理组及SO_2与As联合处理组,检测5 mg·m~(-3) SO_2和/或5 mg·L~(-1) As暴露对小鼠肝脏氧化应激指标、炎症信号通路及肝脏组织结构的影响.结果发现,饮水As暴露组小鼠产生氧化应激损伤,并激活炎症信号通路,导致小鼠肝脏损伤;As与SO_2联合组氧化应激水平高于As或SO_2单独暴露组,炎症信号通路NF-κB及STAT-3的关键因子显著上调表达,肝组织结构损伤加重.研究表明,SO_2会加重As暴露引发的肝脏氧化应激与炎性反应,两者间联合效应促进了肝脏组织结构的损伤.
Arsenic(As) and sulfur dioxide(SO_2) are two environmental pollutants which has been shown to induce liver injury. In recent years, due to increased pollution, humans are often exposed to As, and SO_2. The effects of As and SO_2 co-exposure on mice liver injury and its possible mechanism were studied in this paper. C57 BL/6 mice were selected as the tested animals, and were divided into control group, As treatment group, SO_2 treatment group and SO_2-As co-exposure group. The expression levels of NF-κB and STAT-3 and morphology of mouse livers were observed after sulfur dioxide(5 mg·m~(-3)) and/or arsenic(5 mg·L~(-1)) exposure for 30 days. Compared with control group, As or SO_2 both could cause liver injury, and interestingly, As and SO_2 co-exposure induced more serious injuries via promoting oxidative stress and inflammatory responses. The expression levels of downstream genes in the NF-κB and STAT-3 pathways were higher in mice livers in the co-exposure group than in the groups of As or SO_2 exposure alone. The present results indicates that SO_2-As co-exposure induces more serious injuries compared with As or SO_2 exposure alone.
Arsenic(As) and sulfur dioxide(SO_2) are two environmental pollutants which has been shown to induce liver injury. In recent years, due to increased pollution, humans are often exposed to As, and SO_2. The effects of As and SO_2 co-exposure on mice liver injury and its possible mechanism were studied in this paper. C57 BL/6 mice were selected as the tested animals, and were divided into control group, As treatment group, SO_2 treatment group and SO_2-As co-exposure group. The expression levels of NF-κB and STAT-3 and morphology of mouse livers were observed after sulfur dioxide(5 mg·m~(-3)) and/or arsenic(5 mg·L~(-1)) exposure for 30 days. Compared with control group, As or SO_2 both could cause liver injury, and interestingly, As and SO_2 co-exposure induced more serious injuries via promoting oxidative stress and inflammatory responses. The expression levels of downstream genes in the NF-κB and STAT-3 pathways were higher in mice livers in the co-exposure group than in the groups of As or SO_2 exposure alone. The present results indicates that SO_2-As co-exposure induces more serious injuries compared with As or SO_2 exposure alone.
引文
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周宗灿.2015.氧化还原信号和氧化应激/还原应激[J].毒理学杂志,29(1):1-14
Zhu Y P,Xi S H,Li M Y,et al.2017.Fluoride and arsenic exposure affects spatial memory and activates the ERK/CREB signaling pathway in offspring rats[J].Neurotoxicology,59:56-64
Bai J,Meng Z.2010.Expression of caspase and apoptotic signal pathway induced by sulfur dioxide[J].Environmental and Molecular Mutagenesis,51(2):112-122
Chakraborti D,Rahman M M,Das B,et al.2017.Groundwater arsenic contamination and its health effects in India[J].Hydrogeology Journal,25(4):1165-1181
Chen C J.2014.Health hazards and mitigation of chronic poisoning from arsenic in drinking water:Taiwan experiences[J].Reviews on Environmental Health,29(1/2):13-19
Choudhury S,Ghosh S,Mukherjee S,et al.2016.Pomegranate protects against arsenic-induced p53-dependent ROS-mediated inflammation and apoptosis in liver cells[J].Journal of Clinical Biochemistry and Nutrition,38:25-40
Curtis B J,Shults J A,Boe D M,et al.2019.Mesenchymal stem cell treatment attenuates liver and lung inflammation after ethanol intoxication and burn injury[J].Alcohol, DOI: 1016/J.alcohol.2018.09.001
George C M,Inauen J,Perin J,et al.2017.Behavioral determinants of switching to arsenic-safe water wells:An analysis of a randomized controlled trial of health education interventions coupled with water arsenic testing[J].Health Education and Behavior,44(1):92-102
Ghatak S,Biswas A,Dhali G K,et al.2011.Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice[J].Toxicology and Applied Pharmacology,251(1):59-69
Hong Y S,Song K H,Chung J Y.2014.Health effects of chronic arsenic exposure[J].Journal of Preventive Medicine and Public Health,47(5):245-252
Khodayar M J,Javadipour M,Keshtzar E,et al.2016.Role of berberine against arsenic induced oxidative damage in isolated rat liver[J].Journal of Environmental Biology,37(2):285-290
James K A,Byers T,Hokanson J E,et al.2015.Association between lifetime exposure to inorganic arsenic in drinking water and coronary heart disease in Colorado residents[J].Environmental Health Perspect,123(2):128-134
Jomova K,Jenisova Z,Feszterova M,et al.2011.Arsenic:toxicity,oxidative stress and human disease[J].Journal of Applied Toxicology,31(2):95-107
Kim Y J,Kim J M.2015.Arsenic toxicity in male reproduction and development[J].Development & Reproduction,19:167-180
Kotyzova D,Bludovska M,Eybl V.2013.Differential influences of various arsenic compounds on antioxidant defense system in liver and kidney of rats[J].Environmental Toxicology and Pharmacology,36(3):1015-1021
Li X,Huang L,Wang N,et al.2018.Sulfur dioxide exposure enhances Th2 inflammatory responses via activating STAT6 pathway in asthmatic mice[J].Toxicology Letters,285:43-50
Liang C,Gao Y,Zhao Y,et al.2018.Effects of fluoride and/or sulfur dioxide on morphology and DNA integrity in rats′ hepatic tissue[J].Biological Trace Element Research,183(2):335-341
Meng Z.2003.Oxidative damage of sulfur dioxide on various organs of mice:Sulfur dioxide is a systemic oxidative damage agent[J].Inhalation Toxicology,15(2):181-195
Monaco C,Andreakos E,Kiriakidis S,et al.2004.Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis[J].Proceedings of the National Academy of Sciences of the United States of America,101(15):5634-5639
Rana T,Bera A K,Bhattacharya D,et al.2015.Characterization of arsenic-induced cytotoxicity in liver with stress in erythrocytes and its reversibility with Pleurotus florida lectin[J].Toxicology and Industrial Health,31(2):108-122
Rehman K,Naranmandura H.2012.Arsenic metabolism and thioarsenicals[J].Metallomics,4(9):881-892
Sies H.2015.Oxidative stress:a concept in redox biology and medicine[J].Redox Biology,4:180-183
汤洁,卞建民,李昭阳,等.2013.中国饮水型砷中毒区的水化学环境与砷中毒关系[J].生态毒理学报,8(2):222-229
Tong L,Li K,Zhou Q X.2015.The association between air pollutants and morbidity for diabetes and liver diseases modified by sexes,ages,and seasons in Tianjin,China[J].Environmental Science and Pollution Research,22(2):1215-1219
Vlahopoulos S A.2017.Aberrant control of NF-kappa B in cancer permits transcriptional and phenotypic plasticity,to curtail dependence on host tissue:molecular mode[J].Cancer Biology & Medicine,14(3):254-270
王燕,何大梽.2017.我国废气排放的空间分布与影响因素研究[J].西部论坛,27(6):42-48
周宗灿.2015.氧化还原信号和氧化应激/还原应激[J].毒理学杂志,29(1):1-14
Zhu Y P,Xi S H,Li M Y,et al.2017.Fluoride and arsenic exposure affects spatial memory and activates the ERK/CREB signaling pathway in offspring rats[J].Neurotoxicology,59:56-64