Glyphosate-based herbicides modulate oxidative stress response in the nematode Caenorhabditis elegans (original) (raw)
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Glyphosate-based herbicides and oxidative stress
2021
Since glyphosate became one of the most used herbicides worldwide, its constant release into the environment has raised concern among the general public and international regulatory agencies. Traces of this compound have been detected in fresh and processed food and in environmental matrices. Although there is still controversy about the impact of glyphosate and glyphosate-based herbicides on human health, increasing scientific evidence shows that oxidative stress triggered by these compounds is the main factor responsible for cell damage. Modulation of oxidative stress caused by the imbalance between reactive oxygen species production and induction of antioxidant defense systems has been related to the etiology of several chronic and degenerative ailments such as liver and kidney disorders and neurodegenerative, cardiovascular, and respiratory diseases. This chapter analyzes the impact of glyphosate and glyphosate-based herbicides on environmental and human health with special emph...
Toxicity of atrazine- and glyphosate-based formulations on Caenorhabditis elegans
Ecotoxicology and Environmental Safety, 2018
Atrazine and Glyphosate are herbicides massively used in agriculture for crop protection. Upon application, they are available to the biota in different ecosystems. The aim of this research was to evaluate the toxicity of Glyphosate and Atrazine based formulations (GBF and ABF, respectively). Caenorhabditis elegans was exposed to different concentrations of each single formulation, and to the mixture. Lethality, locomotion, growth, and fertility were measured as endpoints. Effects on gene expression were monitored utilizing green fluorescence protein transgenic strains. ABF caused lethality of 12%, 15%, and 18% for 6, 60, and 600 μM, respectively, displaying a dose dependence trend. GBF produced lethality of 20%, 50%, and 100% at 0.01, 10, and 100 μM, respectively. Locomotion inhibition ranged from 21% to 89% at the lowest and maximum tested concentrations for Atrazine; whereas for Glyphosate, exposure to 10 μM inhibited 87%. Brood size was decreased by 67% and 93% after treatment to 0.06 and 6 μM Atrazine, respectively; and by 23% and 93% after exposure to 0.01 and 10 μM Glyphosate, respectively. There were no significant differences in growth. Changes in gene expression occurred in all genes, highlighting the expression of sod-1, sod-4, and gpx-4 that increased more than twofold after exposure to 600 μM ABF and 10 μM GBF. The effects observed for the mixture of these formulations were additive for lethality, locomotion and fertility. In short, GBF, ABF, and their mixture induced several toxic responses related to oxidative stress on C. elegans.
Glyphosate Caused Detrimental Changes in Enzymatic Antioxidants in Rats
Journal of Pharmaceutical Research International
Background: Glyphosate is the most enormously used broad spectrum herbicide in the world. Current assessment of carcinogenic capability of glyphosate-based herbicides by various regional, national, and international agencies have endangered the controversy. Antioxidant enzymes are often used as biomarkers of oxidative stress. Among the biomarkers superoxide dismutase, catalase and glutathione peroxidase were essential in conservation of homeostasis of cell to function as normal being. Aim: To investigate glyphosate induced detrimental changes in the enzymatic antioxidants in experimental rats. Materials and Methods: Adult male wistar albino rats were divided into 4 groups, each consisting of 6 animals. Group 1 consists of Normal control rats, Group 2 consists of Glyphosate treated at a dose of 50mg/kg body weight/day. Group 3 consists of Glyphosate treated at a dose of 100 mg/kg body weight/day. Group 4 consists of Glyphosate treated at a dose of 250 mg/kg body weight/day. The exper...
Environment International, 2020
Glyphosate-containing herbicides are the most used agrochemicals in the world. Their indiscriminate application raises some concerns regarding the possible health and environmental hazards. In this study, we investigated in human neuroblastoma cell line SH-SY5Y if oxidative stress, altered neurodevelopment and cell death pathways are involved in response to glyphosate and its metabolite aminomethylphosphonic acid (AMPA) exposures. MTT and LDH assays were carried out to assess the glyphosate and AMPA cytotoxicity. Lipid peroxides measured as malondialdehyde (MDA), nitric oxide (NO) and reactive oxygen species (ROS) production, and caspase-Glo 3/7 activity were evaluated. The neuroprotective role of melatonin (MEL), Trolox, N-acetylcysteine (NAC) and Sylibin against glyphosate-and AMPA-induced oxidative stress was examined. Glyphosate and AMPA effects on neuronal development related gene transcriptions, and gene expression profiling of cell death pathways by Real-Time PCR array were also investigated. Glyphosate (5 mM) and AMPA (10 mM) induced a significant increase in MDA levels, NO and ROS production and caspase 3/7 activity. Glyphosate exposure induced
Matters
Glyphosate is a widely-used herbicide that is frequently found as a pollutant of soil and water runoffs. Glyphosate toxicity is controversial but a toxic synergy with other molecules could result in deleterious consequences for living organisms and for the human health. Using budding yeast (Saccharomyces cerevisiae) as a eukaryotic model organism, we report here a strong toxic synergy between glyphosate and 2,4-dinitrophenol (DNP), a phenolic compound derived from diesel engine's combustion and industrial pollutant found frequently in surface water and rainfall. Glyphosate concentrations below 600 mg/L did not affect yeast growth but exhibit dose-dependent toxicity in the presence of non-toxic DNP concentrations (below 1 mM). This so-called 'cocktail effect' increases with DNP concentration. Yeast growth is totally abolished in the presence of the highest concentration of both molecules. We explored the implication of oxidative stress in this synergistic effect of glyphosate and DNP, by measuring H 2 O 2 concentrations in the culture media, and by comparing cta1∆/ctt1∆ catalase double-mutant with wild-type yeast. We did not find any glyphosate-DNP enhanced susceptibility for the catalase mutant and did not observe any clear increase of H 2 O 2 in the presence of the pollutant mixture. All these data suggest that the redox homeostasis is not involved in this toxic synergy, that remains to be explained.
International Journal of Molecular Sciences
Glyphosate is widely used worldwide as a potent herbicide. Due to its ubiquitous use, it is detectable in air, water and foodstuffs and can accumulate in human biological fluids and tissues representing a severe human health risk. In plants, glyphosate acts as an inhibitor of the shikimate pathway, which is absent in vertebrates. Due to this, international scientific authorities have long-considered glyphosate as a compound that has no or weak toxicity in humans. However, increasing evidence has highlighted the toxicity of glyphosate and its formulations in animals and human cells and tissues. Thus, despite the extension of the authorization of the use of glyphosate in Europe until 2022, several countries have begun to take precautionary measures to reduce its diffusion. Glyphosate has been detected in urine, blood and maternal milk and has been found to induce the generation of reactive oxygen species (ROS) and several cytotoxic and genotoxic effects in vitro and in animal models d...
Arhiv za higijenu rada i toksikologiju, 2018
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...
Glyphosate exposure and urinary oxidative stress biomarkers in the Agricultural Health Study
JNCI: Journal of the National Cancer Institute
Background Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study. Methods This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male nonfarmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2′-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α, and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable line...
Ecotoxicology of Glyphosate and Glyphosate-Based Herbicides — Toxicity to Wildlife and Humans
Toxicity and Hazard of Agrochemicals, 2015
The use of agrochemicals, especially herbicides, is necessary to control pests in order to produce adequate food for the global population (estimated at 7 billion). Glyphosate and glyphosate-based herbicides have been used extensively for this purpose but recent studies have reported these chemical substances to be found in aquatic ecosystems, wildlife and humans in various quantities. In this chapter, we reviewed the impacts of glyphosate and glyphosate-based herbicides on wildlife and humans using measured endpoint effects caused by genotoxicity, cytotoxicity and reproductive toxicity. We used findings from different current investigations to demonstrate adverse effects, or otherwise, of glyphosate exposure to wildlife and humans. Our review reveals that glyphosate and its formulations may not only be considered as having genotoxic, cytotoxic or endocrine disrupting properties but they may also be causative agents of reproduction abnormalities in both wildlife and humans. Furthermore, the extensive use of glyphosate-based herbicides in genetically modified glyphosate-resistant plants grown for food and feed should be of grave concern since they can be sources of genotoxicity, cytotoxicity, and reproductive toxicity in wildlife and humans.
Zenodo (CERN European Organization for Nuclear Research), 2021
Background. Health effects from exposure to glyphosate-based herbicides is an intense matter of debate. Toxicity including genotoxicity of glyphosate alone has been repeatedly tested over the last 40 years. Contrastingly, few studies have conducted comparative investigations between glyphosate and its commercial herbicide formulations, such as Roundup. We thus performed the first in-depth comparative toxicogenomic evaluation of glyphosate and a typical European Union Roundup formulation by determining alterations in transcriptome and epigenome profiles. Methods. Glyphosate and the European Union reference commercial formulation Roundup MON 52276 (both at 0.5, 50, 175 mg/kg bw/day glyphosate equivalent concentration) were administered to rats in a subchronic 90-day toxicity study. Standard clinical biochemistry and kidney and liver histopathology was performed. In addition, transcriptomics and DNA methylation profiling of liver and selective gene expression analysis of kidneys was conducted. Furthermore, a panel of six mouse embryonic reporter stem cell lines validated to identify carcinogenic outcomes (DNA damage, oxidative stress, and protein misfolding) were used to provide insight into the mechanisms underlying the toxicity of glyphosate and 3 Roundup formulations. Results. Histopathology and serum biochemistry analysis showed that MON 52276 but not glyphosate treatment was associated with a statistically significant increase in hepatic steatosis and necrosis. Similar lesions were also present in the liver of glyphosate-treated groups but not in the control group. MON 52276 altered the expression of 96 genes in liver, with the most affected biological functions being TP53 activation by DNA damage and oxidative stress as well as the regulation of circadian rhythms. The most affected genes in liver also had their expression similarly altered in kidneys. DNA methylation profiling of liver revealed 5,727 and 4,496 differentially methylated CpG sites between the control group and the group of rats exposed to glyphosate and MON 52276, respectively. Direct DNA damage measurement by apurinic/apyrimidinic lesion formation in liver was increased with glyphosate exposure. Mechanistic evaluations showed that two Roundup herbicides but not glyphosate activated oxidative stress and misfolded protein responses. Conclusions. Taken together, the results of our study show that Roundup herbicides are more toxic than glyphosate, activating mechanisms involved in cellular carcinogenesis and causing gene expression changes reflecting DNA damage. This further highlights the power of high-throughput 'omics' methods to detect metabolic changes, which would be missed by relying solely on conventional biochemical and histopathological measurements. Our study paves the way for future investigations by reporting a panel of gene expression changes and DNA methylation sites, which can serve as biomarkers and potential predictors of negative health outcomes resulting from exposure to glyphosate-based herbicides.