Glyphosate: Hepatotoxicity, Nephrotoxicity, Hemotoxicity, Carcinogenicity, and Clinical Cases of Endocrine, Reproductive, Cardiovascular, and Pulmonary System Intoxication.

Abstract

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.