Glyphosate Commercial Formulation Causes Cytotoxicity, Oxidative Effects, and Apoptosis on Human Cells

Chaufan, Gabriela; Coalova, Isis; Molina, Marı́a del Carmen

doi:10.1177/1091581813517906

Cited by 90 publications

(42 citation statements)

References 53 publications

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“…Cytotoxicity: G and TN-20 aggravate mitochondrial damage and induce apoptosis and necrosis. TN-20 seems to disrupt the integrity of the cellular barrier to G uptake, promoting Gmediated toxicity TN-20 but not G ↘ Bcl-2 or Bax expression; Mixed with G at 0.85 mg/L Bcl-2 expression ↘ and Bax expression ↗ as the TN-20 concentration ↗; ↗ Caspases 3/7 expression (0.4 mg/L TN-20 alone or plus 0.8-1.7 mg/L G); Caspases activity decreases at higher TN-20 concentrations because of necrosis; ↘ mitochondrial membrane potential by G when added to TN-20 apoptotic nuclear changes for G alone (Chaufan et al, 2014) Table 3. Overview of the toxicological properties in mammals of known GlyBH adjuvants.…”

Section: Acknowledgmentsmentioning

confidence: 99%

Potential toxic effects of glyphosate and its commercial formulations below regulatory limits

Mesnage¹,

Defarge²,

Vendômois³

et al. 2015

Food and Chemical Toxicology

413

274

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Glyphosate-based herbicides (GlyBH), including Roundup, are the most widely used pesticides worldwide. Their uses have increased exponentially since their introduction on the market. Residue levels in food or water, as well as human exposures, are escalating. We have reviewed the toxic effects of GlyBH measured below regulatory limits by evaluating the published literature and regulatory reports. We reveal a coherent body of evidence indicating that GlyBH could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects. It includes teratogenic, tumorigenic and hepatorenal effects. They could be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time. Some effects were detected in the range of the recommended acceptable daily intake. Toxic effects of commercial formulations can also be explained by GlyBH adjuvants, which have their own toxicity, but also enhance glyphosate toxicity. These challenge the assumption of safety of GlyBH at the levels at which they contaminate food and the environment, albeit these levels may fall below regulatory thresholds. Neurodevelopmental, reproductive, and transgenerational effects of GlyBH must be revisited, since a growing body of knowledge suggests the predominance of endocrine disrupting mechanisms caused by environmentally relevant levels of exposure.

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Section: Acknowledgmentsmentioning

confidence: 99%

Potential toxic effects of glyphosate and its commercial formulations below regulatory limits

Mesnage¹,

Defarge²,

Vendômois³

et al. 2015

Food and Chemical Toxicology

413

274

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show abstract

“…With the increased use of glyphosate-containing herbicides, such as Touchdown ® (TD; Syngenta) and Roundup ® (Monsanto), many current studies are finally beginning to examine the potential toxicity of the commercially available formulations, and not just the active ingredient or the putative surfactants and associated vehicle(s) [14,32,38]. Using C. elegans as a model organism, our lab has focused on the potential neurotoxicity of TD, as obtainable by industrial and household pesticide applicators [45,46].…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, data from our lab suggest that Caenorhabditis elegans ( C. elegans ) exposed to various concentrations of a commercially available formation of TD results in apparent neurodegeneration, particularly of DAergic neurons [46]. As the use of this herbicide group has increased, so has the interest in the verifying whether differential toxicity actually exists between the commercial formulation and active ingredient [14,51]. …”

Section: 0 Introductionmentioning

confidence: 99%

Exposure of C. elegans eggs to a glyphosate-containing herbicide leads to abnormal neuronal morphology

McVey

Snapp

Johnson

et al. 2016

Neurotoxicology and Teratology

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Recent data demonstrate that chronic exposure of Caenorhabditis elegans (C. elegans) to a high-use glyphosate-containing herbicide, Touchdown (TD), potentially damages the adult nervous system. It is unknown, however, whether unhatched worms exposed to TD during the egg stage show abnormal neurodevelopment post-hatching. Therefore, we investigated whether early treatment with TD leads to aberrant neuronal or neurite development in C. elegans. Studies were completed in three different worm strains with green fluorescent protein (GFP)-tagged neurons to facilitate visual neuronal assessment. Initially, eggs from C. elegans with all neurons tagged with GFP were chronically exposed to TD. Visual inspection suggested decreased neurite projections associated with ventral nerve cord neurons. Data analysis showed a statistically significant decrease in overall green pixel numbers at the fourth larval (L4) stage (*p < 0.05). We further investigated whether specific neuronal populations were preferentially vulnerable to TD by treating eggs from worms that had all dopaminergic (DAergic) or γ-aminobutyric acid (GABAergic) neurons tagged with GFP. As before, green pixel number associated with these discrete neuronal populations was analyzed at multiple larval stages. Data analysis indicated statistically significant decreases in pixel number associated with DAergic, but not GABAergic, neurons (***p< 0.001) at all larval stages. Finally, statistically significant decreases (at the first larval stage, L1) or increases (at the fourth larval stage, L4) in superoxide levels, a developmental signaling molecule, were detected (*p < 0.05). These data suggest that early exposure to TD may impair neuronal development, perhaps through superoxide perturbation. Since toxic insults during development may late render individuals more vulnerable to neurodegenerative diseases in adulthood, these studies provide some of the first evidence in this model organism that early exposure to TD may adversely affect the developing nervous system.

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“…This system is composed of non-enzymatic antioxidants such as ascorbic acid (vitamin C), alpha-tocopherol (vitamin E) and GSH, and enzymatic antioxidants such as superoxide dismutase, catalase and glutathione peroxidase (Birben et al, 2012;Shim et al, 2015;Valko et al, 2015). GSH is an important intracellular antioxidant that scavenges ROS, thus preventing inflammation and cell damage (Chaufan et al, 2014;Tajima et al, 2010). γ-Glutamylcysteine synthetase is a rate-limiting enzyme for the synthesis of GSH.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress and cytotoxic effects of silver ion in mouse lung macrophages J774.1 cells

Shim

Choi

Hirano

2016

J of Applied Toxicology

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Silver is commonly used as a disinfectant, and chronic exposure to silver may cause argyria, resulting in a gray-blue discoloration of human skin. However, the mechanism for cellular toxicity of silver has not been well explained. We studied the mode of cell death, the ratio of glutathione disulfide/glutathione, induction of metallothionein and activation of mitogen-activated protein kinases in J774.1 cells together with activation of antioxidant responsive element and nuclear factor-κB in CHO cells following exposure to silver ion (Ag ) to investigate the mechanism by which Ag causes lethal effects. Ag increased phosphorylation levels of extracellular signal-regulated, c-Jun N-terminal and p38 mitogen-activated protein kinases and remarkably increased the ratio of glutathione disulfide/glutathione in both a time- and concentration-dependent manner. Luciferase reporter gene assays revealed that antioxidant responsive element and nuclear factor-κB were activated following exposure to Ag . In addition, exposure to Ag increased the mRNA and protein levels of metallothionein. We investigated whether or not Ag killed J774.1 cells by inducing apoptosis. Ag increased the activity of caspase-3/7 which was abrogated by caspase 3 and pan-caspase inhibitors. However, these inhibitors did not ameliorate the cytotoxic effects of Ag , suggesting that Ag causes oxidative stress, which leads to necrotic rather than apoptotic cell death in J774.1 cells by decreasing functional sulfhydryl groups including glutathione in the cells. Copyright © 2016 John Wiley & Sons, Ltd.

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Glyphosate Commercial Formulation Causes Cytotoxicity, Oxidative Effects, and Apoptosis on Human Cells

Cited by 90 publications

References 53 publications

Potential toxic effects of glyphosate and its commercial formulations below regulatory limits

Potential toxic effects of glyphosate and its commercial formulations below regulatory limits

Exposure of C. elegans eggs to a glyphosate-containing herbicide leads to abnormal neuronal morphology

Oxidative stress and cytotoxic effects of silver ion in mouse lung macrophages J774.1 cells

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