Stürtz Nelson, Deis Ricardo P, Jahn Graciela A, Duffard Ricardo, Evangelista de Duffard Ana María
Laboratorio de Toxicología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 570, 2000 Rosario, Argentina.
Toxicology. 2008 May 21;247(2-3):73-9. doi: 10.1016/j.tox.2008.02.001. Epub 2008 Feb 13.
Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) has several deleterious effects on the nervous system such as alterations in the concentrations of neurotransmitters in the brain and/or behavioral changes, myelination rate, ganglioside pattern [Bortolozzi, A., Duffard, R., Antonelli, M., Evangelista de Duffard, A.M., 2002. Increased sensitivity in dopamine D(2)-like brain receptors from 2,4-dichlorophenoxyacetic acid (2,4-D)-exposed and amphetamine-challenged rats. Ann. N.Y. Acad. Sci. 965, 314-323; Duffard, R., García, G., Rosso, S., Bortolozzi, A., Madariaga, M., DiPaolo, O., Evangelista de Duffard, A.M., 1996. Central nervous system myelin deficit in rats exposed to 2,4-dichlorophenoxyacetic acid throughout lactation. Neurotoxicol. Teratol. 18, 691-696; Evangelista de Duffard, A.M., Orta, C., Duffard, R., 1990. Behavioral changes in rats fed a diet containing 2,4-dichlorophenoxyacetic butyl ester. Neurotoxicology 11, 563-572; Evangelista de Duffard, A.M., Bortolozzi, A., Duffard, R.O., 1995. Altered behavioral responses in 2,4-dichlorophenoxyacetic acid treated and amphetamine challenged rats. Neurotoxicology 16, 479-488; Munro, I.C., Carlo, G.L., Orr, J.C., Sund, K., Wilson, R.M. Kennepohl, E. Lynch, B., Jablinske, M., Lee, N., 1992. A comprehensive, integrated review and evaluation of the scientific evidence relating to the safety of the herbicide 2,4-D. J. Am. Coll. Toxicol. 11, 559-664; Rosso et al., 2000], and its administration to pregnant and lactating rats adversely affects litter growth and milk quality. Since normal growth of the offspring depends on adequate maternal nursing and care, we evaluated the effect of 2,4-D on rat maternal behavior as well as the dam's monoamine levels in arcuate nucleus (AcN) and serum prolactin (PRL) levels. Wistar dams were exposed to the herbicide through the food from post partum day (PPD) 1 to PPD 7. Dams were fed either with a 2,4-D treated diet (15, 25 or 50mg 2,4-D/kg/daybw) or with a control diet. We observed that maternal nesting behavior was not modified by 2,4-D treatment. However, mother-pup interactions, specially the nursing behavior, were altered. Retrieval, crouching and licking of pups were reduced or suspended after 2,4-D treatment. We also observed an increase in the latency of retrieval and crouching in the dams treated with the herbicide. Dams showed movement along cage peripheries, food consumption during the light phase and high self-grooming. In addition of the deficits observed in maternal behavior parameters, increased catecholamine levels and a drastic decrease in indolamine levels in the AcN of treated dams were determined. Serum PRL levels were also diminished by 62%, 68% and 70% with respect to control dams in the 15, 25 and 50mg 2,4-D/kgbw treated dams, respectively. In conclusion, exposure to 2,4-D during the first post partum days produced changes in maternal behavior, serum prolactin and monoamine levels in the AcN of treated dams.
接触2,4-二氯苯氧乙酸(2,4-D)会对神经系统产生多种有害影响,如大脑中神经递质浓度的改变和/或行为变化、髓鞘形成速率、神经节苷脂模式[博托洛齐,A.,杜法德,R.,安东内利,M.,埃万杰利斯塔·德·杜法德,A.M.,2002年。2,4-二氯苯氧乙酸(2,4-D)暴露和苯丙胺激发的大鼠中多巴胺D(2)样脑受体敏感性增加。《纽约科学院学报》965,314 - 323;杜法德,R.,加西亚,G.,罗索,S.,博托洛齐,A.,马达里亚加,M.,迪保罗,O.,埃万杰利斯塔·德·杜法德,A.M.,1996年。哺乳期全程暴露于2,4-二氯苯氧乙酸的大鼠中枢神经系统髓鞘缺陷。《神经毒理学与致畸学》18,691 - 696;埃万杰利斯塔·德·杜法德,A.M.,奥尔塔,C.,杜法德,R.,1990年。喂食含2,4-二氯苯氧乙酸丁酯饮食的大鼠行为变化。《神经毒理学》11,563 - 572;埃万杰利斯塔·德·杜法德,A.M.,博托洛齐,A.,杜法德,R.O.,1995年。2,4-二氯苯氧乙酸处理和苯丙胺激发的大鼠行为反应改变。《神经毒理学》16,479 - 488;芒罗,I.C.,卡洛,G.L.,奥尔,J.C.,桑德,K.,威尔逊,R.M.,肯内波尔,E.,林奇,B.,贾布林斯克,M.,李,N.,1992年。关于除草剂2,4-D安全性的科学证据的全面综合综述与评估。《美国毒理学杂志》11,559 - 664;罗索等人,2000年],并且给怀孕和哺乳期大鼠施用2,4-D会对窝仔生长和乳汁质量产生不利影响。由于后代的正常生长依赖于母体充足的哺育和照料,我们评估了2,4-D对大鼠母性行为以及母鼠弓状核(AcN)中的单胺水平和血清催乳素(PRL)水平的影响。从产后第1天(PPD)到PPD 7,将Wistar母鼠通过食物暴露于该除草剂。母鼠分别喂食2,4-D处理的饮食(15、25或50毫克2,4-D/千克/天体重)或对照饮食。我们观察到2,4-D处理并未改变母性筑巢行为。然而,母鼠与幼崽的互动,特别是哺育行为,发生了改变。2,4-D处理后,找回、蹲伏和舔舐幼崽的行为减少或停止。我们还观察到用该除草剂处理的母鼠找回和蹲伏的潜伏期增加。母鼠表现出沿着笼子周边移动、在光照阶段进食以及过度自我梳理。除了在母性行为参数中观察到的缺陷外,还测定了处理过的母鼠弓状核中儿茶酚胺水平升高以及吲哚胺水平急剧下降。与对照母鼠相比,在15、25和50毫克2,4-D/千克体重处理的母鼠中,血清催乳素水平也分别降低了62%、68%和70%。总之,产后最初几天接触2,4-D会导致处理过的母鼠母性行为、血清催乳素和弓状核中单胺水平发生变化。