Cytotoxic effects of Roundup Classic and its components on NE-4C and MC3T3-E1 cell lines determined by biochemical and flow cytometric assays

Oláh, Marianna; Farkas, Enikő; Székács, Inna; Horváth, Róbert; Székacs, András

doi:10.1016/j.toxrep.2022.04.014

Cited by 10 publications

(7 citation statements)

References 76 publications

(91 reference statements)

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“…Moreover, the individual toxicity of numerous additives has also been published [ 74 , 75 , 76 ], among which the first generation of polyethoxylated amines has been the focus recently. As a result of numerous independent studies [ 74 , 77 , 78 , 79 ], this surfactant-type was banned in 2016 as a co-formulant in the European Union and was progressively replaced by other surfactants, ethoxylated etheramines, which exhibited lower toxicity on non-target organisms [ 80 , 81 ]. For both, the composition of the preparations and the physico-chemical characteristics of the additives were different, which exerted significantly different toxic effects.…”

Section: Discussionmentioning

confidence: 99%

Ecotoxicological Evaluation of Safener and Antimicrobial Additives in Isoxaflutole-Based Herbicide Formulations

Takács,

Lázár,

Siakwa

et al. 2024

Toxics

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The environmental load by isoxaflutole and its formulated herbicide products has increasingly become apparent because, after the ban of atrazine, isoxaflutole has become its replacement active ingredient (a.i.). Obtaining information regarding the fate of this a.i. in environmental matrices and its ecotoxicological effects on aquatic organisms is essential for the risk assessment of the herbicide. In this study, the effects of Merlin Flexx- and Merlin WG75 formulated isoxaflutole-based herbicide products and two selected additives (cyprosulfamide safener and 1,2-benzisothiazol-3(2H)-one antimicrobial agent) were investigated on Raphidocelis subcapitata in growth inhibition assays. In ecotoxicological tests, two conventional (optical density and chlorophyll-a content) and two induced fluorescence-based (Fv*/Fp: efficiency of the photosystem PSII and Rfd* changes in the observed ratio of fluorescence decrease) endpoints were determined by UV-spectrophotometer and by our FluoroMeter Module, respectively. Furthermore, dissipation of isoxaflutole alone and in its formulated products was examined by an HPLC-UV method. In ecotoxicological assays, the fluorescence-based Rfd* was observed as the most sensitive endpoint. In this study, the effects of the safener cyprosulfamide and the antimicrobial agent 1,2-benzisothiazol-3(2H)-one on R. subcapitata is firstly reported. The results indicated that the isoxaflutole-equivalent toxicity of the mixture of the isoxaflutole–safener–antimicrobial agent triggered lower toxicity (EC50 = 2.81 ± 0.22 mg/L) compared to the individual effect of the a.i. (EC50 = 0.02 ± 0.00 mg/L). The Merlin Flexx formulation (EC50 = 27.04 ± 1.41 mg/L) was found to be approximately 50-fold less toxic than Merlin WG75, which can be explained by the different chemical characteristics and quantity of additives in them. The additives influenced the dissipation of the a.i. in Z8 medium, as the DT50 value decreased by approximately 1.2- and 3.5-fold under light and dark conditions, respectively.

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Section: Discussionmentioning

confidence: 99%

Ecotoxicological Evaluation of Safener and Antimicrobial Additives in Isoxaflutole-Based Herbicide Formulations

Takács,

Lázár,

Siakwa

et al. 2024

Toxics

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“…Cell cycle analysis was performed using the Muse™ Cell Cycle kit [69][70][71]. As recommended by the manufacturer, treated and untreated cells were suspended in ice-cold 70% ethanol and incubated at −20 • C overnight.…”

Section: Cell Cycle Analysismentioning

confidence: 99%

“…The cell distribution across the various cell cycle phases depends on the cell type, cell size, and the initial DNA content. The MUSE Analyzer automatically defines the cell cycle phase based on the cell population's gating, which depends on fluorescence intensity and cell size[69][70][71]. In this regard, tunicamycin increased the accumulation of ER-stressed cells in the G0/G1 phase of the cell cycle, and decreased the number of cells in the G2/Mitosis phase, compared to control (Figure3C).…”

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confidence: 99%

Extracellular Vesicles Isolated from Equine Adipose-Derived Stromal Stem Cells (ASCs) Mitigate Tunicamycin-Induced ER Stress in Equine Corneal Stromal Stem Cells (CSSCs)

Meissner,

Chmielińska,

Ofri

et al. 2024

CIMB

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Corneal ulcers, characterized by severe inflammation of the cornea, can lead to serious, debilitating complications and may be vision-threatening for horses. In this study, we aimed to investigate the role of endoplasmic reticulum (ER) stress in corneal stem progenitor cell (CSSC) dysfunction and explore the potential of equine adipose-derived stromal stem cell (ASC)-derived extracellular vesicles (EVs) to improve corneal wound healing. We showed that CSSCs expressed high levels of CD44, CD45, and CD90 surface markers, indicating their stemness. Supplementation of the ER-stress-inducer tunicamycin to CSSCs resulted in reduced proliferative and migratory potential, accumulation of endoplasmic reticulum (ER)-stressed cells in the G0/G1 phase of the cell cycle, increased expression of proinflammatory genes, induced oxidative stress and sustained ER stress, and unfolded protein response (UPR). Importantly, treatment with EVs increased the proliferative activity and number of cells in the G2/Mitosis phase, enhanced migratory ability, suppressed the overexpression of proinflammatory cytokines, and upregulated the anti-inflammatory miRNA-146a-5p, compared to control and/or ER-stressed cells. Additionally, EVs lowered the expression of ER-stress master regulators and effectors (PERK, IRE1, ATF6, and XBP1), increased the number of mitochondria, and reduced the expression of Fis-1 and Parkin, thereby promoting metabolic homeostasis and protecting against apoptosis in equine CSSCs. Our findings demonstrate that MSCs-derived EVs represent an innovative and promising therapeutic strategy for the transfer of bioactive mediators which regulate various cellular and molecular signaling pathways.

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“…In this regard there has been a major focus on studying the toxicity of GBHs, which are extensively used in agriculture, forestry, urban and domestic settings [14]. Compared to just glyphosate, GBHs can cause more oxidative stress [15,16], more DNA damage [17,18], and be more toxic [19], which changes the risk profile of this herbicide. GBHs have also been demonstrated to cause more reproductive [20][21][22] or hepatotoxic [23,24] effects as well as gut microbiome composition changes [25] compared to glyphosate alone.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity Mechanisms of Eight Major Herbicide Active Ingredients in Comparison to Their Commercial Formulations

Ferguson

Mesnage

Antoniou

2022

Toxics

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Commercial pesticide formulations contain co-formulants, which are generally considered as having no toxic effects in mammals. This study aims to compare the toxicity of 8 major herbicide active ingredients–namely glyphosate, dicamba, 2,4-D, fluroxypyr, quizalofop-p-ethyl, pendimethalin, propyzamide and metazachlor–with a typical commercial formulation of each active ingredient. Cytotoxicity and oxidative stress capability was assessed in human hepatoma HepG2 cells. Using an MTT assay, formulations of glyphosate (Roundup Probio), fluroxypyr (Hurler), quizalofop-p-ethyl (Targa Super) and dicamba (Hunter) were more toxic than the active ingredient alone. Metazachlor and its formulation Sultan had similar cytotoxicity profiles. Cytotoxicity profiles were comparable in immortalised human fibroblasts. Toxilight necrosis assays showed the formulation of metazachlor (Sultan50C) resulted in significant membrane disruption compared to the active ingredient. Generation of reactive oxygen species was detected for glyphosate, fluroxypyr, pendimethalin, quizalofop-p-ethyl, the formulation of 2,4-D (Anti-Liserons), and dicamba and its formulation Hunter. Further testing of quizalofop-p-ethyl and its formulation Targa Super in the ToxTracker assay system revealed that both products induced oxidative stress and an unfolded protein response. In conclusion, these results show that most herbicide formulations tested in this study are more toxic than their active ingredients in human tissue culture cell model systems. The results add to a growing body of evidence, which implies that commercial herbicide formulations and not just their active ingredients should be evaluated in regulatory risk assessment of pesticides.

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Cytotoxic effects of Roundup Classic and its components on NE-4C and MC3T3-E1 cell lines determined by biochemical and flow cytometric assays

Cited by 10 publications

References 76 publications

Ecotoxicological Evaluation of Safener and Antimicrobial Additives in Isoxaflutole-Based Herbicide Formulations

Ecotoxicological Evaluation of Safener and Antimicrobial Additives in Isoxaflutole-Based Herbicide Formulations

Extracellular Vesicles Isolated from Equine Adipose-Derived Stromal Stem Cells (ASCs) Mitigate Tunicamycin-Induced ER Stress in Equine Corneal Stromal Stem Cells (CSSCs)

Cytotoxicity Mechanisms of Eight Major Herbicide Active Ingredients in Comparison to Their Commercial Formulations

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