Chávez-Reyes Jesús, Saráchaga-Terrazas Fernando, Colis-Arenas Oliver Alejandro, López-Lariz Carlos H, Villalón Carlos M, Marichal-Cancino Bruno A
Department of Physiology and Pharmacology, Centre of Basic Sciences, Autonomous University of Aguascalientes, Ciudad Universitaria 940, Aguascalientes 20100, Mexico.
Department of Medicine, Centre of Health Sciences, Autonomous University of Aguascalientes, Ciudad Universitaria 940, Aguascalientes 20100, Mexico.
J Xenobiot. 2024 May 7;14(2):604-612. doi: 10.3390/jox14020035.
Glyphosate, a widely used herbicide, is linked to a plethora of deleterious effects in both clinical and preclinical studies. Nevertheless, the effects of its main metabolite, aminomethylphosphonic acid (AMPA), whose half-life in soil is even longer than that of glyphosate, have been little explored. On this basis, as a first approach, in this work, we report that intraperitoneal (i.p.) administration of AMPA or glyphosate (at 10, 56, and 100 mg/kg) decreased, to a similar extent, plasma cholinesterase (ChE) activity in acutely exposed rats. Moreover, we designed an experimental protocol to analyze and compare the effects of AMPA and glyphosate on human plasma ChE activity; this protocol consisted of adding these compounds to human plasma to subsequently test the effects of this plasma on the contraction to acetylcholine (ACh) in the frog rectus abdominis muscle (an indirect estimate of ChE activity). Accordingly, this muscular contraction to ACh was evaluated before and after pre-incubation of ACh with (i) plasma alone, (ii) plasma with AMPA, and (iii) plasma with glyphosate. Our results indicate that AMPA, like glyphosate, decreased ChE activity in the plasma of rats (when given i.p.) and humans (when added in vitro), suggesting that both xenobiotics may exert similar toxicological effects.
草甘膦是一种广泛使用的除草剂，在临床和临床前研究中与大量有害影响有关。然而，其主要代谢物氨甲基膦酸（AMPA）的影响却鲜有研究，AMPA在土壤中的半衰期甚至比草甘膦更长。在此基础上，作为第一步，在本研究中，我们报告腹腔注射（i.p.）AMPA或草甘膦（剂量为10、56和100mg/kg）在急性暴露的大鼠中同等程度地降低了血浆胆碱酯酶（ChE）活性。此外，我们设计了一个实验方案来分析和比较AMPA和草甘膦对人血浆ChE活性的影响；该方案包括将这些化合物添加到人血浆中，随后测试该血浆对青蛙腹直肌中乙酰胆碱（ACh）收缩的影响（ChE活性的间接估计）。因此，在ACh与（i）单独血浆、（ii）含AMPA的血浆和（iii）含草甘膦的血浆预孵育之前和之后，评估了对ACh的肌肉收缩情况。我们的结果表明，AMPA与草甘膦一样，降低了大鼠（腹腔注射时）和人类（体外添加时）血浆中的ChE活性，这表明这两种外源性物质可能产生相似的毒理学效应。
