Milić Mirta, Žunec Suzana, Micek Vedran, Kašuba Vilena, Mikolić Anja, Lovaković Blanka Tariba, Semren Tanja Živković, Pavičić Ivan, Čermak Ana Marija Marjanović, Pizent Alica, Vrdoljak Ana Lucić, Valencia-Quintana Rafael, Sánchez-Alarcón Juana, Želježić Davor
Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Laboratorio "Rafael Villalobos-Pietrini" de Toxicología Genómica y Química Ambiental, Facultad de Agrobiología, Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico.
Arh Hig Rada Toksikol. 2018 Jun 1;69(2):154-168. doi: 10.2478/aiht-2018-69-3114.
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.
在这项为期28天的研究中，我们评估了通过灌胃给予Wistar大鼠草甘膦除草剂的影响，其每日剂量相当于可接受的操作人员接触水平（AOEL）的0.1、消费者可接受的每日摄入量（ADI）的0.5、1.75（对应于慢性人群调整剂量，cPAD）以及10毫克/千克体重（bw）（对应于AOEL的100倍）。在每次处理结束时，测量体重和肝脏重量，并与它们的基线值进行比较。使用碱性彗星试验估计白细胞和肝脏组织中的DNA损伤。通过一系列终点评估氧化应激，以通过硫代巴比妥酸反应性物质（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）活性来确定脂质过氧化。还测量了总胆碱酯酶活性以及乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的活性。暴露的动物体重增加比对照组少。处理导致肝细胞和白细胞中的原发性DNA损伤显著更高。草甘膦暴露显著降低了AOEL、ADI和cPAD组肝脏中的TBARS，以及AOEL和cPAD组血浆中的TBARS。所有处理均抑制了AChE，但AOEL和ADI组与对照组有显著差异。总ChE以及血浆/肝脏ROS/GSH水平与对照组无显著差异，除了AOEL和ADI组中ChE降低35%以及cPAD和100xAOEL组中肝脏GSH显著下降。AOEL和ADI组血液中GSH-Px活性显著下降，但在肝脏中，ADI、cPAD和100xAOEL组与对照组相比显著增加。所有这些发现表明，即使暴露于低水平的草甘膦也可能产生严重的不利影响，并指出需要改变对低水平慢性/亚慢性草甘膦暴露风险评估的方法，在这种情况下，氧化应激不一定与遗传损伤和AChE抑制相关。
