Oxidative stress, cholinesterase activity, and DNA damage in the liver, whole blood, and plasma of Wistar rats following a 28-day exposure to glyphosate
Oxidative stress, cholinesterase activity, and DNA damage in the liver, whole blood, and plasma of Wistar rats following a 28-day exposure to glyphosate
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DOI：
10.2478/aiht-2018-69-3114
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发表时间：
2018-06-01
影响因子：
2.1
通讯作者：
Zeljezic, Davor
中科院分区：
文献类型：
--
作者：
Milic, Mirta;Zunec, Suzana;Zeljezic, Davor
在这项为期28天的研究中，我们评估了对Wistar大鼠灌胃施用除草剂草甘膦的影响，每日剂量相当于操作者可接受接触水平（AOEL）的0.1、消费者可接受每日摄入量（ADI）的0.5、（相当于慢性人群调整剂量，cPAD）和10毫克/千克体重（相当于操作人员接触水平的100倍）。在每次治疗结束时，测量体重和肝脏重量，并与其基线值进行比较。用碱性彗星试验检测白细胞和肝组织DNA损伤。使用一组终点评价氧化应激，以通过硫代巴比妥反应物质（TBARS）水平、活性氧（ROS）水平、谷胱甘肽（GSH）水平和谷胱甘肽过氧化物酶（GSH-Px）活性建立脂质过氧化。同时测定总胆碱酯酶活性、乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）活性。暴露动物的体重增加少于对照组。治疗导致肝细胞和白细胞中的原发性DNA损伤显著增加。在操作人员接触水平、每日允许摄入量和cPAD组中，暴露于草甘膦可显著降低肝脏中的TBARS，在操作人员接触水平和cPAD组中，暴露于草甘膦可显著降低血浆中的TBARS。AChE在所有处理中均受到抑制，但AOEL和ADI组与对照组差异显著。总胆碱酯酶和血浆/肝脏活性氧/谷胱甘肽水平与对照组相比没有显著差异，除了操作人员接触水平和每日允许摄入量组的胆碱酯酶下降35%，以及cPAD和100倍操作人员接触水平组的肝脏谷胱甘肽显著下降。AOEL和ADI使血液中GSH-Px活性显著下降，而肝脏中ADI、cPAD则显著升高。和100 xAOEL组与对照组。所有这些研究结果表明，即使暴露于低水平的草甘膦也会产生严重的不良影响，并指出需要改变低水平慢性/亚慢性草甘膦暴露的风险评估方法，其中氧化应激不一定与遗传损伤和乙酰胆碱酯酶抑制有关。
In this 28 day-study, we evaluated the effects of herbicide glyphosate administered by gavage to Wistar rats at daily doses equivalent to 0.1 of the acceptable operator exposure level (AOEL), 0.5 of the consumer acceptable daily intake (ADI), 1.75 (corresponding to the chronic population-adjusted dose, cPAD), and 10 mg kg(-1) body weight (bw) (corresponding to 100 times the AOEL). At the end of each treatment, the body and liver weights were measured and compared with their baseline values. DNA damage in leukocytes and liver tissue was estimated with the alkaline comet assay. Oxidative stress was evaluated using a battery of endpoints to establish lipid peroxidation via thiobarbituric reactive substances (TBARS) level, level of reactive oxygen species (ROS), glutathione (GSH) level, and the activity of glutathione peroxidase (GSH-Px). Total cholinesterase activity and the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were also measured. The exposed animals gained less weight than control. Treatment resulted in significantly higher primary DNA damage in the liver cells and leukocytes. Glyphosate exposure significantly lowered TBARS in the liver of the AOEL, ADI, and cPAD groups, and in plasma in the AOEL and cPAD group. AChE was inhibited with all treatments, but the AOEL and ADI groups significantly differed from control. Total ChE and plasma/liver ROS/GSH levels did not significantly differ from control, except for the 35 % decrease in ChE in the AOEL and ADI groups and a significant drop in liver GSH in the cPAD and 100xAOEL groups. AOEL and ADI blood GSH-Px activity dropped significantly, but in the liver it significantly increased in the ADI, cPAD. and 100xAOEL groups vs. control. All these findings show that even exposure to low glyphosate levels can have serious adverse effects and points to a need to change the approach to risk assessment of low-level chronic/sub-chronic glyphosate exposure, where oxidative stress is not necessarily related to the genetic damage and AChE inhibition.