Mazuryk Jarosław, Klepacka Katarzyna, Kutner Włodzimierz, Sharma Piyush Sindhu
Department of Electrode Processes, Institute of Physical Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland.
Bio & Soft Matter, Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, 1 Place Louis Pasteur, 1348 Louvain-la-Neuve, Belgium.
ACS Pharmacol Transl Sci. 2024 Apr 8;7(5):1205-1236. doi: 10.1021/acsptsci.4c00046. eCollection 2024 May 10.
Glyphosate (GLP) is an active agent of GLP-based herbicides (GBHs), i.e., broad-spectrum and postemergent weedkillers, commercialized by Monsanto as, e.g., Roundup and RangerPro formulants. The GBH crop spraying, dedicated to genetically engineered GLP-resistant crops, has revolutionized modern agriculture by increasing the production yield. However, abusively administered GBHs' ingredients, e.g., GLP, polyoxyethyleneamine, and heavy metals, have polluted environmental and industrial areas far beyond farmlands, causing global contamination and life-threatening risk, which has led to the recent local bans of GBH use. Moreover, preclinical and clinical reports have demonstrated harmful impacts of GLP and other GBH ingredients on the gut microbiome, gastrointestinal tract, liver, kidney, and endocrine, as well as reproductive, and cardiopulmonary systems, whereas carcinogenicity of these herbicides remains controversial. Occupational exposure to GBH dysregulates the hypothalamic-pituitary-adrenal axis, responsible for steroidogenesis and endocrinal secretion, thus affecting hormonal homeostasis, functions of reproductive organs, and fertility. On the other hand, acute intoxication with GBH, characterized by dehydration, oliguria, paralytic ileus, as well as hypovolemic and cardiogenic shock, pulmonary edema, hyperkalemia, and metabolic acidosis, may occur fatally. As no antidote has been developed for GBH poisoning so far, the detoxification is mainly symptomatic and supportive and requires intensive care based on gastric lavage, extracorporeal blood filtering, and intravenous lipid emulsion infusion. The current review comprehensively discusses the molecular and physiological basics of the GLP- and/or GBH-induced diseases of the endocrine and reproductive systems, and cardiopulmonary-, nephro-, and hepatotoxicities, presented in recent preclinical studies and case reports on the accidental or intentional ingestions with the most popular GBHs. Finally, they briefly describe modern and future healthcare methods and tools for GLP detection, determination, and detoxification. Future electronically powered, decision-making, and user-friendly devices targeting major GLP/GBH's modes of actions, i.e., dysbiosis and the inhibition of AChE, shall enable self-handled or point-of-care professional-assisted evaluation of the harm followed with rapid capturing GBH xenobiotics in the body and precise determining the GBH pathology-associated biomarkers levels.
草甘膦（GLP）是基于草甘膦的除草剂（GBHs）的活性成分，即广谱芽后除草剂，孟山都公司将其商业化，例如农达和RangerPro配方剂。专门用于转基因抗草甘膦作物的GBH作物喷洒，通过提高产量彻底改变了现代农业。然而，滥用GBHs的成分，如草甘膦、聚氧乙烯胺和重金属，已经污染了远远超出农田的环境和工业区，造成全球污染和危及生命的风险，这导致最近局部地区禁止使用GBH。此外，临床前和临床报告表明，草甘膦和其他GBH成分对肠道微生物群、胃肠道、肝脏、肾脏以及内分泌、生殖和心肺系统有有害影响，而这些除草剂的致癌性仍存在争议。职业接触GBH会使负责类固醇生成和内分泌分泌的下丘脑-垂体-肾上腺轴失调，从而影响激素稳态、生殖器官功能和生育能力。另一方面，GBH急性中毒的特征是脱水、少尿、麻痹性肠梗阻以及低血容量性和心源性休克、肺水肿、高钾血症和代谢性酸中毒，可能会致命。由于目前尚未开发出针对GBH中毒的解毒剂，解毒主要是对症和支持性的，需要基于洗胃、体外血液过滤和静脉注射脂质乳剂输注的重症监护。本综述全面讨论了最近临床前研究以及关于意外或故意摄入最常用GBHs的病例报告中呈现的草甘膦和/或GBH引起的内分泌和生殖系统疾病以及心肺、肾和肝毒性的分子和生理基础。最后，他们简要描述了用于草甘膦检测、测定和解毒的现代及未来医疗保健方法和工具。未来针对主要草甘膦/GBH作用模式（即生态失调和乙酰胆碱酯酶抑制）的电子驱动、决策性和用户友好型设备，将能够进行自我处理或现场专业辅助的危害评估，随后快速捕获体内的GBH外源性物质并精确测定与GBH病理相关的生物标志物水平。
