新生鼠暴露亚中毒阈剂量毒死蜱诱导脑组织氧化损伤
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摘要
目的:研究新生鼠暴露亚中毒阈剂量毒死蜱(chlorpyrifos,CPF)诱导脑组织氧化损伤情况,探讨CPF导致神经发育毒性的作用机制。
方法:出生11天SD大鼠108只,随机分为CPF组(n=36)、对照组(n=72)。对照组又分为溶媒二甲亚砜(Dimethysulfoxide,DMSO)对照组(n=36)和生理盐水(Normal Saline,NS)对照组(n=36)。大鼠出生后11-14天,连续经腹部皮下注射亚中毒阈剂量(以下简称“亚剂量”,5mg/kg.d)CPF,制作新生SD大鼠暴露亚剂量CPF动物模型,对照组分别以DMSO、NS替代CPF。所有大鼠在最后一次注药后12小时、24小时、72小时三个时间点分别被处死,并立即取脑,期间严密观察大鼠是否有急性有机磷农药中毒症状。用可见分光光度法测定脑组织匀浆超氧化物岐化酶(SOD)活性和丙二醛(MDA)含量变化;免疫组织化学和Western Blotting方法检测脑蛋白羰基表达变化情况。所有数据用均值±标准差((?)±S)表示,所有资料采用SPSS12.0统计软件包进行数据处理。
结果:
1.新生鼠暴露亚剂量CPF未见急性有机磷农药中毒症状。
2.脑组织匀浆MDA含量发生改变,CPF组与两对照组比较,数值增高,差异有统计学意义(P＜0.05)。
3.脑组织匀浆SOD含量发生改变,CPF组与两对照组比较,数值减少,差异有统计学意义(P＜0.05)。
4.CPF组与对照组比较,脑组织蛋白羰基含量增加。特别是免疫组织化学方法检测下丘脑层面,差异有统计学意义(P＜0.05)。
结论:1.新生鼠暴露亚中毒阈剂量CPF可诱导脑组织氧化损伤;2.氧化应激是CPF导致神经发育毒性的作用机制之一。
Objective: To explore the oxidative damage effects on postnatal rats exposed to subthreshold doses of chlorpyrifos and the mechanisms of CPF caused development neurotoxicity.
Methods: Postnatal 11 days SD rats (n = 108) were randomly divided in to CPF group (n = 36) and control group (n = 72).The control group were then further divided into dimethysulfoxide (DMSO, n = 36) group and normal saline group (NS, n = 36). Postnatal 11-14 days rats were injected with CPF at subthreshold doses for overt systemic toxicity (5 mg/kg/day). The control groups were injected the same doses of DMSO or saline instead. The animals were sacrificed respectively at 12 h, 24 h and 72 h after the final injection and the brains were collected immediately. The Acute organophosphorus pesticide intoxication symptom of the rats was monitored at the above three time points. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the rat brain homogenate were detected by spectrophotometry. Immunohistochemistry assay and Western Blotting assay were taken to detect the expression of protein carbonyl. All data were expressed as the mean±SEM. All data were analyzed using statistic software SPSS v12.0.
Results:
1. Exposed to subthreshold doses of CPF did not produce any acute organophosphorus pesticide intoxication symptoms.
2. The content of MDA in the rat brain homogenate was changed. The CPF group had more MDA than the control groups (p<0.05).
3. The content of SOD in the rat brain homogenate was changed. The CPF group had less SOD than the control groups (p<0.05).
4. The CPF group had more protein carbonyl than the control group, especially in the hypothalamus detected by the Immunohistochemistry assay. There was significant difference (p<0.05).
Conclusions: 1. Exposed to subthreshold doses of chlorpyrifos on postnatal rats can cause oxidative damage;
2. Oxidative stress is one of the mechanisms of CPF caused development neurotoxicity.
方法:出生11天SD大鼠108只,随机分为CPF组(n=36)、对照组(n=72)。对照组又分为溶媒二甲亚砜(Dimethysulfoxide,DMSO)对照组(n=36)和生理盐水(Normal Saline,NS)对照组(n=36)。大鼠出生后11-14天,连续经腹部皮下注射亚中毒阈剂量(以下简称“亚剂量”,5mg/kg.d)CPF,制作新生SD大鼠暴露亚剂量CPF动物模型,对照组分别以DMSO、NS替代CPF。所有大鼠在最后一次注药后12小时、24小时、72小时三个时间点分别被处死,并立即取脑,期间严密观察大鼠是否有急性有机磷农药中毒症状。用可见分光光度法测定脑组织匀浆超氧化物岐化酶(SOD)活性和丙二醛(MDA)含量变化;免疫组织化学和Western Blotting方法检测脑蛋白羰基表达变化情况。所有数据用均值±标准差((?)±S)表示,所有资料采用SPSS12.0统计软件包进行数据处理。
结果:
1.新生鼠暴露亚剂量CPF未见急性有机磷农药中毒症状。
2.脑组织匀浆MDA含量发生改变,CPF组与两对照组比较,数值增高,差异有统计学意义(P＜0.05)。
3.脑组织匀浆SOD含量发生改变,CPF组与两对照组比较,数值减少,差异有统计学意义(P＜0.05)。
4.CPF组与对照组比较,脑组织蛋白羰基含量增加。特别是免疫组织化学方法检测下丘脑层面,差异有统计学意义(P＜0.05)。
结论:1.新生鼠暴露亚中毒阈剂量CPF可诱导脑组织氧化损伤;2.氧化应激是CPF导致神经发育毒性的作用机制之一。
Objective: To explore the oxidative damage effects on postnatal rats exposed to subthreshold doses of chlorpyrifos and the mechanisms of CPF caused development neurotoxicity.
Methods: Postnatal 11 days SD rats (n = 108) were randomly divided in to CPF group (n = 36) and control group (n = 72).The control group were then further divided into dimethysulfoxide (DMSO, n = 36) group and normal saline group (NS, n = 36). Postnatal 11-14 days rats were injected with CPF at subthreshold doses for overt systemic toxicity (5 mg/kg/day). The control groups were injected the same doses of DMSO or saline instead. The animals were sacrificed respectively at 12 h, 24 h and 72 h after the final injection and the brains were collected immediately. The Acute organophosphorus pesticide intoxication symptom of the rats was monitored at the above three time points. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the rat brain homogenate were detected by spectrophotometry. Immunohistochemistry assay and Western Blotting assay were taken to detect the expression of protein carbonyl. All data were expressed as the mean±SEM. All data were analyzed using statistic software SPSS v12.0.
Results:
1. Exposed to subthreshold doses of CPF did not produce any acute organophosphorus pesticide intoxication symptoms.
2. The content of MDA in the rat brain homogenate was changed. The CPF group had more MDA than the control groups (p<0.05).
3. The content of SOD in the rat brain homogenate was changed. The CPF group had less SOD than the control groups (p<0.05).
4. The CPF group had more protein carbonyl than the control group, especially in the hypothalamus detected by the Immunohistochemistry assay. There was significant difference (p<0.05).
Conclusions: 1. Exposed to subthreshold doses of chlorpyrifos on postnatal rats can cause oxidative damage;
2. Oxidative stress is one of the mechanisms of CPF caused development neurotoxicity.
引文
[1]Ted Schettler.Toxic threats to neurologic development of children.Environ Health Perspect.2001,109(6):813-816.
[2]Koger SM,Schettler T,Weiss B.Environmental toxicants and developmental disabilities:a challenge for psychologists.Am Psychol,2005,60(3):243-255.
[3]Goldman LR,Koduru S.Chemicals in the environment and developmental toxicity to children:a public health and policy perspective.Environ Health Perspect,2000,108(3):443-448.
[4]陶梦华,金凡.1972-1998年上海市区小儿恶性肿瘤发病趋势.肿瘤,2001,219(6):426-430.
[5]梅秀元,鹿占成.病残儿神经精神类疾病的病因分析与优生指导.中国优生于遗传杂志,2003,11(4):124-125.
[6]Grandjean P,Landrigan PJ.Developmental neur.otoxicity of industrial chemi cals.Lancet,2006,368(953):2167-78.
[7]顾中言,许小龙,韩丽娟.我国农药应用技术现状、发展趋势和需解决的关键问题.江苏农药,2001(2):9-11.
[8]T.A.Slotkin,C.A.Tate,Cousins MM,et al.Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure.Developmental Brain Research,2002,133:163-173.
[9]田文学,张桂玺,李西东.毒死蜱的研究进展.山东农药信息,2006,8:18-20.
[10]李小鹰,王爱芬.毒死蜱及其防治白蚁效果与应用研究进展综述.白蚁科技,1996,13(3):11-19.
[11]Hill R.H,Jr,et al.Pesticide residues in urine of adults living in the United States:reference range concentrations.Environ Res.1995;71:99-108.
[12]T.Colborn.A case for revisiting the safety of pesticides:a closer look at neurodevelopment.Environ.Health Perspect,2006,114(1):10-17.
[13]L.G.Costa.Current issues in organophosphate toxicology.Clin.Chim Acta,2006,366(1-2):1-13.
[14]P.J.Landrigan,L.Claudio,S.B Markowitz,et al.Pesticides and inner-city children:exposures,risks,and prevention.Environ.Health Perspect,1999,107(S3):431-437.
[15]B.Weiss,S.Amler,R.W.Amler.Pesticides.Pediatrics,2004,113:1030-1036.
[16]Levin ED,Addy N,Nakajima A,et al.Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats.Brain Res Dev Brain Res,2001,130(1):83-89.
[17]Ricceri L,Markina N,Valanzano A,et al.Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice.Toxicol Appl Pharmacol,2003,191(3):189-201.
[18]邓礼(研究生),赵玲玲(导师).亚中毒阈剂量毒死蜱对新生SD大鼠脑小胶质细胞的影响.中南大学硕士研究生论文库,2006.
[19]赵玲玲.新生鼠暴露亚中毒阈剂量毒死蜱诱导黑质多巴胺能神经元损伤和神经行为改变.中南大学博士研究生论文库,2006.
[20]L.Crumpton F.J.Seidler,T.A.Slotldn.Is oxidative stress involved in the developmental neurotoxicity of chlorpyfifos? Developental Brain Research,2000,121(2):189-195.
[21]Gennaro Giordano,Zhara Afsharinejad,Marina Guizzetti,et al.Organophosphorus insecticides chlorpyfifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency.Toxicology and Applied Pharmacology,2007,219(2-3):181-189.
[22]Theodore A.Slotkin,Colleen A.Oliver,Frederic J.Seidler.Critical periods for the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos and terbutaline,alone or in combination.Brain Res Dev Brain Res,2005,157(2):172-180.
[23]S.J.James,W.Slikker,S.Melnyk,et al.Thimerosal neurotoxicity is associated with glutathione depletion:protection with glutathione precursors.Neurotoxicology,2005,26(1):1-8.
[24]Sies H.Oxidative stress:from basic research to clinical application.Am J Med,1991,91(3C):S31-S38.
[25]Peter M,Abuja,Riccardo A.lbertini.Methods for monitoring oxidative stress,lipid peroxidation and oxidation resistance of lipoproteins.Clinica Chimica Acta,2001,306(1-2):1-17.
[26]Keiki Ogino,Da-Hong Wang.Biomarkers of Oxidative/Nitrosafive Stress:An Approach to Disease Prevention.Acta Med,2007,61(4):181-189.
[27]Pantke U,Volk T,Schmutzler M,et al.Oxidized proteins as a marker of oxidative stress during coronary heart surgery.Free Radic Biol Med,1999, 27(9-10):1080-1086.
[28]Zhou JE Cai D,Zhu YG,et al.A study on relationship of nitric oxide,oxidation,peroxidation,lipoperoxidation with chronic cholecystitis.World J Gastroentero,2000,6:501-507.
[29]Zhou JE Zhu YG,Peng FY,et al.Study on relationship of chronic cholecystitis with stone and nitric Oxide oxidation,peroxidation,lipoperoxidation.Am J Comprehen Med,2000,2:260-264.
[30]Zhou JF,Si PL,Ruan ZR,et al.Primary studies on heroin abuse and injury induced by oxidation and lipoperoxidation.Chinese Medical Journal,2001,114(3):297-302.
[31]Tuzmen N,Candan N,Kaya E,Demiryas N.Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver.Cell Biochem Funct,2008,26(1):119-124.
[32]Bebe FN,Myna Panemangalore.Exposure to Low Doses of Endosulfan and Chlorpyrifos Modifies Endogenous Antioxidants in Tissues of Rats.J Environ Sci Health B,2003,38(3):349-363.
[33]Pushpinder Kaur,Bishan Radotra,Ranjana W,et al.Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic dichlorvos (OP)exposure in rat brain.Neurotoxicology,2007,28(6):1208-1219.
[34]单红卫,林军,杨兴易.急性有机磷农药中毒患者血清脂质过氧化物超氧化物歧化酶的变化及意义.中国急救医学,2003,5(23):339-339.
[35]方伟钧,李赵梅,杨建新.急性有机磷农药口服中毒与自由基变化关系的初步探讨.中华急诊医学杂志,2002,11(4):232-235.
[36]Radhey S.Verma,Anugya Mehta,Nalini Srivastava.In vivo chlorpyrifos induced oxidative stress:Attenuation by antioxidant vitamins.Pesticide Biochemistry and Physiology,2007,88(2):191-196.
[37]Ajay Goel,Vijayta Dani,D.K.Dhawan.Protective effects of zinc on lipid peroxidation,antioxidant enzymes and hepatic histoarchitecture in chlorpyrifos induced toxicity.Chem Biol Interact,2005,156(2-3):131-140.
[38]Fatih Gultekin,Namik.Delibas,Sulhattin Yasar,et al.In vivo changes in antioxidant systems and protective role of melatonin and a combination of vitamin C and vitamin E on oxidative damage in erythrocytes induced by chlorpyrifos-ethyl in rats.Arch Toxicol,2001,75(2):88-96.
[39]Hiromichi Shoji,Berthold Koletzko.Oxidative stress and antioxidant protection in the perinatal period.Current Opinion in Clinical Nutrition and Metabolic Care,2007,10(3):324-328.
[40]D.Qiao,F.J.Seidler,TA.Slotkin.Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.Toxicology and Applied Pharmacology,2005,206(1):17-26.
[41]Verma RS.Chlorpyrifos-induced alterations in levels of thiobarbituric acid reactive substances and glutathione in rat brain.Indian J Exp Biol,2001,39(2):174-177.
[42]Claudia M.Testa,Todd B.Sherer J.Timothy Greenamyre.Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures.Molecular Brain Research,2005,134(1):109-118.
[43]Slotkin TA,Seidler FJ.The alterations in CNS serotonergic mechanisms caused by neonatal chlorpyrifos exposure are permanent.Developmental Brain Research,2005,158(1-2):115-119.
[44]Timofeeva OA,Roegge CS,Seidler FJ,et al.Persistent cognitive alterations in rats after early postnatal exposure to low doses of the organophosphate pesticide,diazinon.Neurotoxicol Teratol,2008,30(1):38-45.
[45]崔洁,曹参祥,郑静.脑出血大鼠脑组织MDA、TNF-a含量变化及其依达拉奉干预效应的研究.第三军医大学学报,2007,29(11):1032-1035.
[1]Abou-Donia MB.Organophosphorus ester-induced chronic neurotoxicity.Archives of Environmental Health,2003,58(8):484-497.
[2]孙运光,周志俊.乐果亚急性染毒诱导大鼠耐受以及对大鼠脑组织M受体的影响.环境与职业医学,2003,20(3):154-158.
[3]Slotkin TA,Tate CA,Cousins MM,et al.Functional alterations in CNS catecholamine system in adolescence and adulthood after neonatal chlorpyrifos exposure.Brain Res Der Brain Res,2002,133(2):163-173.
[4]李钦云,赵玲玲.低剂量有机磷农药对中枢神经系统的影响.中华急诊医学杂志,2005,14(4):348-350.
[1]R.C.Gupta.Brain regional heterogeneity and toxicological mechanisms of organophosphates and carbamates.Toxicol Mech Methods,2004,14(3):103-143.
[2]Brocardo PS,Pandolfo P,Takahashi RN,et al.Antioxidant defenses and lipid peroxidation in the cerebral cortex and hippocampus following acute exposure to malathion and/or zinc chloride.Toxicology,2005,207(2):283-291.
[3]M Abdollahi,A Ranjbar,S Shadnia,et al.Pesticides and oxidative stress:a review.Med Sci Monit,2004,10(6):RA141-147.
[4]Abou-Donia MB.Organophosphorus ester-induced chronic neurotoxicity.Archives of Environmental Health,2003,58(8):484-497.
[5]Kovacic P.Mechanism of organophosphates(nerve gases and pesticides)and antidotes:electron transfer and oxidative stress.Curr Med.Chem,2003,10(24):2705-2709.
[6]Banerjee B.D,Seth V,Ahmed R.S.Pesticide induced oxidative stress:perspectives and trends.Rev.Environ Health,2001,16(1):1-40.
[7]Sies H.Oxidative stress:from basic research to clinical application.Am J Med,1991,91(3C):S31-S38.
[8]Butterfield DA.Amyloid beta-peptide(1-42)-induced oxidative stress and neurotoxicity:implications for neurodegeneration in Alzheimer's disease brain. A review.Free Radic Res,2002,36(12):1307-1313.
[9]Butterfield DA,Lauderback CM.Lipid peroxidation and protein oxidation in Alzheimer's disease brain:potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress.Free Rad Biol Med,2002,32(11):1050-1060.
[10]Zarkovic N.4-Hydroxynonenal as a bioactive marker of pathophysiological processes.Mol Aspects Med,2003,24(4-5):281-291.
[11]Beal MF.Oxidatively modified proteins in aging and disease.Free Radic Biol Med,2002,32(9):797-803.
[12]Oberg BP,et al.Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease.Kidney Int,2004,65(3):1009-1016.
[13]海春旭,等.自由基医学.第四军医大学出版社,2006,12.
[14]Chan PH,Kawase M,Murakami K,et al.Over expression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion.J Neurosci,1998,18(20):8292-8299.
[15]Kim GW,Lewen A,Copin J,et al.The cytosolic antioxidant,copper/zinc superoxide dismutase,attenuates blood-brain barrier disruption and oxidative cellular injury after photothrombotic cortical ischemia in mice.Neuroscience,2001,105(4):1007-1018.
[16]Kawase M,Murakami K,Fujimura M,et al.Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency.Stroke,1999,30(9):1962-1968.
[17]Anisimov VN,Zavarzain NY,Zabezhinski MA,et al.Melatonin increases both life span and tumor incidence in female CBA mice.J Gernontol A Biol Sci Med Sci,2001,56(7):311-323.
[18]Ari Barzilai,Ken-Ichi Yamamoto.DNA damage responses to oxidative stress.DNA Repair,2004,3(8-9):1109-1115.
[19]Hsin-Chen Lee,Yau-Huei Wei.Oxidative Stress,Mitochondrial DNA Mutation,and Apoptosis in Aging.Exp Biol Med,2007,232(5):592-606.
[20]Keiki Ogino,Da-Hong Wang.Biomarkers of Oxidative/Nitrosative Stress:An Approach to Disease Prevention.Acta Med,2007,61(4):181-189.
[21]Peter M,Abuja,Riccardo.Methods for monitoring oxidative stress,lipid peroxidation and oxidation resistance of lipoproteins.Clinica Chimica Acta, 2001, 306(1-2): 1-17.
[22] E Schleicher, U Friess. Oxidative stress, AGE, and atherosclerosis.Kidney Int Suppl, 2007, 106(S): 17-26.
[23] B.E. Mileson, J.E Chambers, W.L. Chen, et al.Common mechanism of toxicity: a case study of organophosphorus pesticides.Fundamental and applied toxicology, 1998,41(1):8-20.
[24] C.N. Pope. Organophosphorus pesticides: do they all have the same mechanism of toxicity? Toxicol. Environ. Health, 1999, 2(2): 161-181.
[25] Costa LG Current issues in organophosphate toxicology.Clin Chim Acta, 2006, 366(1-2):1-13.
[26] Sharma Y, Bashir S, Irshad M, et al. Effects of acute dimethoate administration on antioxidant status of liver and brain of experimental rats. Toxicology, 2005,206(1):49-54.
[27] Poovala V.S, Huang H, Salahudeen A.K. Role of oxygen metabolites in organophosphate-bidrin-induced renal tubular cytotoxicity.J. Am. Soc, 1999, 10(8): 1746-1752.
[28] Gultekin F. The effect of organophosphate insecticide chlorpyrifos-ethyl on lipid peroxidation and antioxidant enzymes (in vitro). Arch Toxicol, 2000, 74 (9):533-538.
[29] Gupta RC. Depletion of energy metabolites following acetylcholinesterase inhibitor-induced status epilepticus: protection by antioxidants. Neurotoxic- ology, 2001,22(2):271-282.
[30] Gupta RC. Nitric oxide modulates high-energy phosphates in brain regions of rats intoxicated with diisopropylphosphorofluoridate or carbofuran: prevention by N-tert-butyl-alpha- phenylnitrone or vitamin E. Arch Toxicol, 2001, 75(6): 346-356.
[31] Verma RS. Chlorpyrifos-induced alterations in levels of thiobarbituric acid reactive substances and glutathione in rat brain.Indian J Exp Biol, 2001, 39(2): 174-177.
[32] Akhgari M, Abdollahi M, Kebryaeezadeh A, et al. Biochemical evidence for free adical-induced lipid peroxidation as a mechanism for subchronic toxicity of malathion in blood and liver of rats. Hum Exp Toxicol, 2003, 22:205-211.
[33] Ranjbar A, Pasalar P, Abdollahi M.Induction of oxidative stress and acetylcholinesterase inhibition in organophosphorous pesticide manufacturing workers. Hum Exp Toxicol, 2002,21(4): 179-182.
[34] Dantoine T, Debord J, Merle L, Charmes JP. Roles of Paraoxonase 1 in organophosphate compounds toxicity and in atherosclerosis.Rev Med Interne, 2003, 24(7):436-442.
[35] L.Crumpton EJ. Seidler T.A. Slotkin.Is oxidative stress involved in the developmental neurotoxicity of chlorpyrifos? Developental Brain Research, 2000, 121(2): 189-195.
[36] Pushpinder Kaur, Bishan Radotra, Ranjana W. Minz c,et al.Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic dichlorvos (OP) exposure in rat brain. NeuroToxicology, 2007, 28 (6): 1208-1219.
[37] Claudia M. Testa, Todd B, Sherer J. Timothy Greenamyre.Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Molecular Brain Research, 2005,134(1):109-118.
[38] Theodore A, Slotkin, Colleen A. Oliver, Frederic J.Seidler.Critical periods for the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos and terbutaline, alone or in combination.Brain Res Dev Brain Res, 2005, 157(2):172-180.
[39] D.Qiao, F.J.Seidler, TA. Slotkin.Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.Toxicology and Applied Pharmacology, 2005, 206(1): 17-26.
[40] S.J. James, W. Slikker, S. Melnyk, et al.Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursors. Neurotoxic- ology, 2005,26(1): 1-8.
[41] Gennaro Giordano, Zhara Afsharinejad, Marina Guizzetti, et al. Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency.Toxicology and Applied Pharmacology, 2007, 219(2-3): 181-189.
[42] Tuzmen N, Candan N, Kaya E, Demiryas N. Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver. Cell Biochem Funct, 2008, 26(1): 119-124.
[43] Frederick N. Bebe, Myna Panemangalore. Exposure to Low Doses of Endosulfan and Chlorpyrifos Modifies Endogenous Antioxidants in Tissues of Rats. J Environ Sci Health B, 2003, 38(3):349-363.
[44]单红卫,林军,杨兴易.急性有机磷农药中毒患者血清脂质过氧化物超氧化物歧化酶的变化及意义.中国急救医学,2003,23(5):339.
[45]方伟钧,李赵梅,杨建新.急性有机磷农药口服中毒与自由基变化关系的初步探讨.中华急诊医学杂志,2002,11(4):232-235.
[46]Ajay Goel,Vijayta Dani,D.K.Dhawan.Protective effects of zinc on lipid peroxidation,antioxidant enzymes and hepatic histoarchitecture in chlorpyrifos induced toxicity.Chem Biol Interact,2005,156(2-3):131-140.
[47]Fatih Gultekin,Namik Delibas,Sulhattin Yasar,et al.In vivo changes in antioxidant systems and protective role of melatonin and a combination of vitamin C and vitamin E on oxidative damage in erythrocytes induced by chlorpyrifos-ethyl in rats.Arch Toxicol,2001,75(2):88-96.
[48]Radhey S.Verma,Anugya Mehta,Nalini Srivastava.In vivo chlorpyrifos induced oxidative stress:Attenuation by antioxidant vitamins.Pesticide Biochemistry and Physiology,2007,88(2):191-196.
[2]Koger SM,Schettler T,Weiss B.Environmental toxicants and developmental disabilities:a challenge for psychologists.Am Psychol,2005,60(3):243-255.
[3]Goldman LR,Koduru S.Chemicals in the environment and developmental toxicity to children:a public health and policy perspective.Environ Health Perspect,2000,108(3):443-448.
[4]陶梦华,金凡.1972-1998年上海市区小儿恶性肿瘤发病趋势.肿瘤,2001,219(6):426-430.
[5]梅秀元,鹿占成.病残儿神经精神类疾病的病因分析与优生指导.中国优生于遗传杂志,2003,11(4):124-125.
[6]Grandjean P,Landrigan PJ.Developmental neur.otoxicity of industrial chemi cals.Lancet,2006,368(953):2167-78.
[7]顾中言,许小龙,韩丽娟.我国农药应用技术现状、发展趋势和需解决的关键问题.江苏农药,2001(2):9-11.
[8]T.A.Slotkin,C.A.Tate,Cousins MM,et al.Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure.Developmental Brain Research,2002,133:163-173.
[9]田文学,张桂玺,李西东.毒死蜱的研究进展.山东农药信息,2006,8:18-20.
[10]李小鹰,王爱芬.毒死蜱及其防治白蚁效果与应用研究进展综述.白蚁科技,1996,13(3):11-19.
[11]Hill R.H,Jr,et al.Pesticide residues in urine of adults living in the United States:reference range concentrations.Environ Res.1995;71:99-108.
[12]T.Colborn.A case for revisiting the safety of pesticides:a closer look at neurodevelopment.Environ.Health Perspect,2006,114(1):10-17.
[13]L.G.Costa.Current issues in organophosphate toxicology.Clin.Chim Acta,2006,366(1-2):1-13.
[14]P.J.Landrigan,L.Claudio,S.B Markowitz,et al.Pesticides and inner-city children:exposures,risks,and prevention.Environ.Health Perspect,1999,107(S3):431-437.
[15]B.Weiss,S.Amler,R.W.Amler.Pesticides.Pediatrics,2004,113:1030-1036.
[16]Levin ED,Addy N,Nakajima A,et al.Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats.Brain Res Dev Brain Res,2001,130(1):83-89.
[17]Ricceri L,Markina N,Valanzano A,et al.Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice.Toxicol Appl Pharmacol,2003,191(3):189-201.
[18]邓礼(研究生),赵玲玲(导师).亚中毒阈剂量毒死蜱对新生SD大鼠脑小胶质细胞的影响.中南大学硕士研究生论文库,2006.
[19]赵玲玲.新生鼠暴露亚中毒阈剂量毒死蜱诱导黑质多巴胺能神经元损伤和神经行为改变.中南大学博士研究生论文库,2006.
[20]L.Crumpton F.J.Seidler,T.A.Slotldn.Is oxidative stress involved in the developmental neurotoxicity of chlorpyfifos? Developental Brain Research,2000,121(2):189-195.
[21]Gennaro Giordano,Zhara Afsharinejad,Marina Guizzetti,et al.Organophosphorus insecticides chlorpyfifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency.Toxicology and Applied Pharmacology,2007,219(2-3):181-189.
[22]Theodore A.Slotkin,Colleen A.Oliver,Frederic J.Seidler.Critical periods for the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos and terbutaline,alone or in combination.Brain Res Dev Brain Res,2005,157(2):172-180.
[23]S.J.James,W.Slikker,S.Melnyk,et al.Thimerosal neurotoxicity is associated with glutathione depletion:protection with glutathione precursors.Neurotoxicology,2005,26(1):1-8.
[24]Sies H.Oxidative stress:from basic research to clinical application.Am J Med,1991,91(3C):S31-S38.
[25]Peter M,Abuja,Riccardo A.lbertini.Methods for monitoring oxidative stress,lipid peroxidation and oxidation resistance of lipoproteins.Clinica Chimica Acta,2001,306(1-2):1-17.
[26]Keiki Ogino,Da-Hong Wang.Biomarkers of Oxidative/Nitrosafive Stress:An Approach to Disease Prevention.Acta Med,2007,61(4):181-189.
[27]Pantke U,Volk T,Schmutzler M,et al.Oxidized proteins as a marker of oxidative stress during coronary heart surgery.Free Radic Biol Med,1999, 27(9-10):1080-1086.
[28]Zhou JE Cai D,Zhu YG,et al.A study on relationship of nitric oxide,oxidation,peroxidation,lipoperoxidation with chronic cholecystitis.World J Gastroentero,2000,6:501-507.
[29]Zhou JE Zhu YG,Peng FY,et al.Study on relationship of chronic cholecystitis with stone and nitric Oxide oxidation,peroxidation,lipoperoxidation.Am J Comprehen Med,2000,2:260-264.
[30]Zhou JF,Si PL,Ruan ZR,et al.Primary studies on heroin abuse and injury induced by oxidation and lipoperoxidation.Chinese Medical Journal,2001,114(3):297-302.
[31]Tuzmen N,Candan N,Kaya E,Demiryas N.Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver.Cell Biochem Funct,2008,26(1):119-124.
[32]Bebe FN,Myna Panemangalore.Exposure to Low Doses of Endosulfan and Chlorpyrifos Modifies Endogenous Antioxidants in Tissues of Rats.J Environ Sci Health B,2003,38(3):349-363.
[33]Pushpinder Kaur,Bishan Radotra,Ranjana W,et al.Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic dichlorvos (OP)exposure in rat brain.Neurotoxicology,2007,28(6):1208-1219.
[34]单红卫,林军,杨兴易.急性有机磷农药中毒患者血清脂质过氧化物超氧化物歧化酶的变化及意义.中国急救医学,2003,5(23):339-339.
[35]方伟钧,李赵梅,杨建新.急性有机磷农药口服中毒与自由基变化关系的初步探讨.中华急诊医学杂志,2002,11(4):232-235.
[36]Radhey S.Verma,Anugya Mehta,Nalini Srivastava.In vivo chlorpyrifos induced oxidative stress:Attenuation by antioxidant vitamins.Pesticide Biochemistry and Physiology,2007,88(2):191-196.
[37]Ajay Goel,Vijayta Dani,D.K.Dhawan.Protective effects of zinc on lipid peroxidation,antioxidant enzymes and hepatic histoarchitecture in chlorpyrifos induced toxicity.Chem Biol Interact,2005,156(2-3):131-140.
[38]Fatih Gultekin,Namik.Delibas,Sulhattin Yasar,et al.In vivo changes in antioxidant systems and protective role of melatonin and a combination of vitamin C and vitamin E on oxidative damage in erythrocytes induced by chlorpyrifos-ethyl in rats.Arch Toxicol,2001,75(2):88-96.
[39]Hiromichi Shoji,Berthold Koletzko.Oxidative stress and antioxidant protection in the perinatal period.Current Opinion in Clinical Nutrition and Metabolic Care,2007,10(3):324-328.
[40]D.Qiao,F.J.Seidler,TA.Slotkin.Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.Toxicology and Applied Pharmacology,2005,206(1):17-26.
[41]Verma RS.Chlorpyrifos-induced alterations in levels of thiobarbituric acid reactive substances and glutathione in rat brain.Indian J Exp Biol,2001,39(2):174-177.
[42]Claudia M.Testa,Todd B.Sherer J.Timothy Greenamyre.Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures.Molecular Brain Research,2005,134(1):109-118.
[43]Slotkin TA,Seidler FJ.The alterations in CNS serotonergic mechanisms caused by neonatal chlorpyrifos exposure are permanent.Developmental Brain Research,2005,158(1-2):115-119.
[44]Timofeeva OA,Roegge CS,Seidler FJ,et al.Persistent cognitive alterations in rats after early postnatal exposure to low doses of the organophosphate pesticide,diazinon.Neurotoxicol Teratol,2008,30(1):38-45.
[45]崔洁,曹参祥,郑静.脑出血大鼠脑组织MDA、TNF-a含量变化及其依达拉奉干预效应的研究.第三军医大学学报,2007,29(11):1032-1035.
[1]Abou-Donia MB.Organophosphorus ester-induced chronic neurotoxicity.Archives of Environmental Health,2003,58(8):484-497.
[2]孙运光,周志俊.乐果亚急性染毒诱导大鼠耐受以及对大鼠脑组织M受体的影响.环境与职业医学,2003,20(3):154-158.
[3]Slotkin TA,Tate CA,Cousins MM,et al.Functional alterations in CNS catecholamine system in adolescence and adulthood after neonatal chlorpyrifos exposure.Brain Res Der Brain Res,2002,133(2):163-173.
[4]李钦云,赵玲玲.低剂量有机磷农药对中枢神经系统的影响.中华急诊医学杂志,2005,14(4):348-350.
[1]R.C.Gupta.Brain regional heterogeneity and toxicological mechanisms of organophosphates and carbamates.Toxicol Mech Methods,2004,14(3):103-143.
[2]Brocardo PS,Pandolfo P,Takahashi RN,et al.Antioxidant defenses and lipid peroxidation in the cerebral cortex and hippocampus following acute exposure to malathion and/or zinc chloride.Toxicology,2005,207(2):283-291.
[3]M Abdollahi,A Ranjbar,S Shadnia,et al.Pesticides and oxidative stress:a review.Med Sci Monit,2004,10(6):RA141-147.
[4]Abou-Donia MB.Organophosphorus ester-induced chronic neurotoxicity.Archives of Environmental Health,2003,58(8):484-497.
[5]Kovacic P.Mechanism of organophosphates(nerve gases and pesticides)and antidotes:electron transfer and oxidative stress.Curr Med.Chem,2003,10(24):2705-2709.
[6]Banerjee B.D,Seth V,Ahmed R.S.Pesticide induced oxidative stress:perspectives and trends.Rev.Environ Health,2001,16(1):1-40.
[7]Sies H.Oxidative stress:from basic research to clinical application.Am J Med,1991,91(3C):S31-S38.
[8]Butterfield DA.Amyloid beta-peptide(1-42)-induced oxidative stress and neurotoxicity:implications for neurodegeneration in Alzheimer's disease brain. A review.Free Radic Res,2002,36(12):1307-1313.
[9]Butterfield DA,Lauderback CM.Lipid peroxidation and protein oxidation in Alzheimer's disease brain:potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress.Free Rad Biol Med,2002,32(11):1050-1060.
[10]Zarkovic N.4-Hydroxynonenal as a bioactive marker of pathophysiological processes.Mol Aspects Med,2003,24(4-5):281-291.
[11]Beal MF.Oxidatively modified proteins in aging and disease.Free Radic Biol Med,2002,32(9):797-803.
[12]Oberg BP,et al.Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease.Kidney Int,2004,65(3):1009-1016.
[13]海春旭,等.自由基医学.第四军医大学出版社,2006,12.
[14]Chan PH,Kawase M,Murakami K,et al.Over expression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion.J Neurosci,1998,18(20):8292-8299.
[15]Kim GW,Lewen A,Copin J,et al.The cytosolic antioxidant,copper/zinc superoxide dismutase,attenuates blood-brain barrier disruption and oxidative cellular injury after photothrombotic cortical ischemia in mice.Neuroscience,2001,105(4):1007-1018.
[16]Kawase M,Murakami K,Fujimura M,et al.Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency.Stroke,1999,30(9):1962-1968.
[17]Anisimov VN,Zavarzain NY,Zabezhinski MA,et al.Melatonin increases both life span and tumor incidence in female CBA mice.J Gernontol A Biol Sci Med Sci,2001,56(7):311-323.
[18]Ari Barzilai,Ken-Ichi Yamamoto.DNA damage responses to oxidative stress.DNA Repair,2004,3(8-9):1109-1115.
[19]Hsin-Chen Lee,Yau-Huei Wei.Oxidative Stress,Mitochondrial DNA Mutation,and Apoptosis in Aging.Exp Biol Med,2007,232(5):592-606.
[20]Keiki Ogino,Da-Hong Wang.Biomarkers of Oxidative/Nitrosative Stress:An Approach to Disease Prevention.Acta Med,2007,61(4):181-189.
[21]Peter M,Abuja,Riccardo.Methods for monitoring oxidative stress,lipid peroxidation and oxidation resistance of lipoproteins.Clinica Chimica Acta, 2001, 306(1-2): 1-17.
[22] E Schleicher, U Friess. Oxidative stress, AGE, and atherosclerosis.Kidney Int Suppl, 2007, 106(S): 17-26.
[23] B.E. Mileson, J.E Chambers, W.L. Chen, et al.Common mechanism of toxicity: a case study of organophosphorus pesticides.Fundamental and applied toxicology, 1998,41(1):8-20.
[24] C.N. Pope. Organophosphorus pesticides: do they all have the same mechanism of toxicity? Toxicol. Environ. Health, 1999, 2(2): 161-181.
[25] Costa LG Current issues in organophosphate toxicology.Clin Chim Acta, 2006, 366(1-2):1-13.
[26] Sharma Y, Bashir S, Irshad M, et al. Effects of acute dimethoate administration on antioxidant status of liver and brain of experimental rats. Toxicology, 2005,206(1):49-54.
[27] Poovala V.S, Huang H, Salahudeen A.K. Role of oxygen metabolites in organophosphate-bidrin-induced renal tubular cytotoxicity.J. Am. Soc, 1999, 10(8): 1746-1752.
[28] Gultekin F. The effect of organophosphate insecticide chlorpyrifos-ethyl on lipid peroxidation and antioxidant enzymes (in vitro). Arch Toxicol, 2000, 74 (9):533-538.
[29] Gupta RC. Depletion of energy metabolites following acetylcholinesterase inhibitor-induced status epilepticus: protection by antioxidants. Neurotoxic- ology, 2001,22(2):271-282.
[30] Gupta RC. Nitric oxide modulates high-energy phosphates in brain regions of rats intoxicated with diisopropylphosphorofluoridate or carbofuran: prevention by N-tert-butyl-alpha- phenylnitrone or vitamin E. Arch Toxicol, 2001, 75(6): 346-356.
[31] Verma RS. Chlorpyrifos-induced alterations in levels of thiobarbituric acid reactive substances and glutathione in rat brain.Indian J Exp Biol, 2001, 39(2): 174-177.
[32] Akhgari M, Abdollahi M, Kebryaeezadeh A, et al. Biochemical evidence for free adical-induced lipid peroxidation as a mechanism for subchronic toxicity of malathion in blood and liver of rats. Hum Exp Toxicol, 2003, 22:205-211.
[33] Ranjbar A, Pasalar P, Abdollahi M.Induction of oxidative stress and acetylcholinesterase inhibition in organophosphorous pesticide manufacturing workers. Hum Exp Toxicol, 2002,21(4): 179-182.
[34] Dantoine T, Debord J, Merle L, Charmes JP. Roles of Paraoxonase 1 in organophosphate compounds toxicity and in atherosclerosis.Rev Med Interne, 2003, 24(7):436-442.
[35] L.Crumpton EJ. Seidler T.A. Slotkin.Is oxidative stress involved in the developmental neurotoxicity of chlorpyrifos? Developental Brain Research, 2000, 121(2): 189-195.
[36] Pushpinder Kaur, Bishan Radotra, Ranjana W. Minz c,et al.Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic dichlorvos (OP) exposure in rat brain. NeuroToxicology, 2007, 28 (6): 1208-1219.
[37] Claudia M. Testa, Todd B, Sherer J. Timothy Greenamyre.Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Molecular Brain Research, 2005,134(1):109-118.
[38] Theodore A, Slotkin, Colleen A. Oliver, Frederic J.Seidler.Critical periods for the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos and terbutaline, alone or in combination.Brain Res Dev Brain Res, 2005, 157(2):172-180.
[39] D.Qiao, F.J.Seidler, TA. Slotkin.Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.Toxicology and Applied Pharmacology, 2005, 206(1): 17-26.
[40] S.J. James, W. Slikker, S. Melnyk, et al.Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursors. Neurotoxic- ology, 2005,26(1): 1-8.
[41] Gennaro Giordano, Zhara Afsharinejad, Marina Guizzetti, et al. Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency.Toxicology and Applied Pharmacology, 2007, 219(2-3): 181-189.
[42] Tuzmen N, Candan N, Kaya E, Demiryas N. Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver. Cell Biochem Funct, 2008, 26(1): 119-124.
[43] Frederick N. Bebe, Myna Panemangalore. Exposure to Low Doses of Endosulfan and Chlorpyrifos Modifies Endogenous Antioxidants in Tissues of Rats. J Environ Sci Health B, 2003, 38(3):349-363.
[44]单红卫,林军,杨兴易.急性有机磷农药中毒患者血清脂质过氧化物超氧化物歧化酶的变化及意义.中国急救医学,2003,23(5):339.
[45]方伟钧,李赵梅,杨建新.急性有机磷农药口服中毒与自由基变化关系的初步探讨.中华急诊医学杂志,2002,11(4):232-235.
[46]Ajay Goel,Vijayta Dani,D.K.Dhawan.Protective effects of zinc on lipid peroxidation,antioxidant enzymes and hepatic histoarchitecture in chlorpyrifos induced toxicity.Chem Biol Interact,2005,156(2-3):131-140.
[47]Fatih Gultekin,Namik Delibas,Sulhattin Yasar,et al.In vivo changes in antioxidant systems and protective role of melatonin and a combination of vitamin C and vitamin E on oxidative damage in erythrocytes induced by chlorpyrifos-ethyl in rats.Arch Toxicol,2001,75(2):88-96.
[48]Radhey S.Verma,Anugya Mehta,Nalini Srivastava.In vivo chlorpyrifos induced oxidative stress:Attenuation by antioxidant vitamins.Pesticide Biochemistry and Physiology,2007,88(2):191-196.