Mapping the key characteristics of carcinogens for glyphosate and its formulations: A systematic review DOI Creative Commons
Iemaan Rana, Patton Khuu Nguyen, Gabrielle Rigutto

et al.

Chemosphere, Journal Year: 2023, Volume and Issue: 339, P. 139572 - 139572

Published: July 18, 2023

Glyphosate was classified as a probable human carcinogen by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic evidence in 2015. Since then, numerous studies of glyphosate and its formulations (GBF) have emerged. These can be evaluated cancer hazard identification with newly described ten key characteristics (KC) carcinogens approach. Our objective assess all vivo, ex vitro experimental animals (mammals) that compared exposure glyphosate/GBF low/no counterparts KCs. A protocol our methods adhering PRISMA guidelines registered priori (INPLASY202180045). Two blinded reviewers screened humans/mammals reporting any KC-related outcome available PubMed before August 2021. Studies met inclusion criteria underwent data extraction conducted duplicate each KC reported along aspects internal/external validity, results, reference information. were used construct matrix subsequently analyzed program R conduct strength quality assessments. Of 2537 articles screened, 175 criteria, from which we extracted >50,000 points related outcomes. Data analysis revealed KC2, KC4, KC5, KC6, KC8, limited KC1 KC3, inadequate KC7, KC9, KC10. Notably, in-depth analyses genotoxicity (KC2) (KC8) endocrine disruption consistent positive findings. For found: 1) humans provided stronger than animal studies; 2) GBF elicited effect both when alone; 3) highest consistently genotoxicity. KC8 indicated glyphosate's ability modulate hormone levels estrogen receptor activity is sensitive concentration formulation. The modulations observed provide clear interacts receptors, alters activation, modulates effects endogenous ligands (including hormones). findings strengthen biological plausibility previously associations humans, such non-Hodgkin lymphoma. We identified potential molecular interactions subsequent events generate pathway lymphomagenesis.

Language: Английский

The SH-SY5Y human neuroblastoma cell line, a relevant in vitro cell model for investigating neurotoxicology in human: Focus on organic pollutants DOI Creative Commons
Lorena Lopez-Suarez, Sana Al Awabdh, Xavier Coumoul

et al.

NeuroToxicology, Journal Year: 2022, Volume and Issue: 92, P. 131 - 155

Published: July 30, 2022

Language: Английский

Citations

138
Glyphosate damages blood-testis barrier via NOX1-triggered oxidative stress in rats: Long-term exposure as a potential risk for male reproductive health DOI Creative Commons
Jingbo Liu, Zifa Li, Lu Lu

et al.

Environment International, Journal Year: 2021, Volume and Issue: 159, P. 107038 - 107038

Published: Dec. 11, 2021

Blood-testis barrier (BTB) creates a privileged niche indispensable for spermatogenesis. Glyphosate (GLY), the most commonly used herbicide worldwide, has been reported to decrease sperm quality. However, whether and how GLY destroys BTB affect quality remains be elucidated. Herein, this study was designed investigate influence of on in vivo vitro experiments. The results showed that male rats exposed 4 months exhibited quantity, accompanied by integrity disruption testicular oxidative stress. Additionally, GLY-induced reactive oxygen species (ROS) contributed downregulation BTB-related proteins primary Sertoli cells (SCs). Intriguingly, we identified marked upregulation stress-related gene NOX1 GLY-exposed testis based transcriptome analysis. knockdown blocked stress, as well prevented protein SCs. Furthermore, estrogen receptor (ER)-α significantly upregulated models. An ER-α inhibitor decreased expression levels both NOX1. Mechanistically, directly interacted with at site Pro39 Lys401 promote activation, which boosted trigger ROS accumulation. Collectively, these demonstrate long-term exposure adversely affects integrity, disrupts spermatogenesis via activation ER-α/NOX1 axis. This presents better understanding risk fertility.

Language: Английский

Citations

125
Toxic Effects of Glyphosate on the Nervous System: A Systematic Review DOI Open Access
Carmen Costas‐Ferreira, R. Durán, L.R.F. Faro

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4605 - 4605

Published: April 21, 2022

Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in world. It can persist environment for days or months, and its intensive large-scale use constitute major environmental health problem. In this systematic review, we investigate current state of our knowledge related to effects pesticide on nervous system various animal species humans. The information provided indicates that exposure glyphosate commercial formulations induces several neurotoxic effects. has been shown during early stages life seriously affect normal cell development by deregulating some signaling pathways involved process, leading alterations differentiation, neuronal growth, myelination. Glyphosate also seems exert significant toxic effect neurotransmission induce oxidative stress, neuroinflammation mitochondrial dysfunction, processes lead death due autophagy, necrosis, apoptosis, as well appearance behavioral motor disorders. doses produce these vary but are lower than limits set regulatory agencies. Although there important discrepancies between analyzed findings, it unequivocal produces structure function humans, rodents, fish, invertebrates.

Language: Английский

Citations

113
Glyphosate Herbicide: Reproductive Outcomes and Multigenerational Effects DOI Creative Commons
María M. Milesi,

Virginia Lorenz,

Milena Durando

et al.

Frontiers in Endocrinology, Journal Year: 2021, Volume and Issue: 12

Published: July 7, 2021

Glyphosate base herbicides (GBHs) are the most widely applied pesticides in world and mainly used association with GBH-tolerant crop varieties. Indiscriminate negligent use of GBHs has promoted emergence glyphosate resistant weeds, consequently rise these herbicides. Glyphosate, active ingredient all GBHs, is combined other chemicals known as co-formulants that enhance herbicide action. Nowadays, safety its formulations remain to be a controversial issue, evidence not conclusive whether adverse effects caused by GBH or glyphosate, little about contribution toxicity Currently, alarmingly increased levels have been detected different environmental matrixes foodstuff, becoming an issue social concern. Some

Language: Английский

Citations

62
Oxidative Stress and Metabolism: A Mechanistic Insight for Glyphosate Toxicology DOI Open Access
Xiaojing Wang, Qirong Lu, Jingchao Guo

et al.

The Annual Review of Pharmacology and Toxicology, Journal Year: 2022, Volume and Issue: 62(1), P. 617 - 639

Published: Jan. 6, 2022

Glyphosate (GLYP) is a widely used pesticide; it considered to be safe herbicide for animals and humans because targets 5-enolpyruvylshikimate-3-phosphate synthase. However, there has been increasing evidence that GLYP causes varying degrees of toxicity. Moreover, oxidative stress metabolism are highly correlated with This review provides comprehensive introduction the toxicity and, first time, systematically summarizes mechanism from perspective stress, including GLYP-mediated damage, changes in antioxidant status, altered signaling pathways, regulation by exogenous substances. In addition, discussed, metabolites,metabolic metabolic enzymes, metabolites. new ideas proposes effective strategies reducing its

Language: Английский

Citations

62
Pharmacological Treatment of Vascular Dementia: A Molecular Mechanism Perspective DOI Creative Commons
Huang Kuang, Zhifeng Zhou,

Yuge Zhu

et al.

Aging and Disease, Journal Year: 2021, Volume and Issue: 12(1), P. 308 - 308

Published: Jan. 1, 2021

Vascular dementia (VaD) is a neurodegenerative disease, with cognitive dysfunction attributable to cerebrovascular factors.At present, it the second most frequently occurring type of in older adults (after Alzheimer's disease).The underlying etiology VaD has not been completely elucidated, which limits its management.Currently, there are no approved standard treatments for VaD.The drugs used only suitable symptomatic treatment and cannot prevent or reduce occurrence progression VaD.This review summarizes current status pharmacological VaD, from perspective molecular mechanisms specified various pathogenic hypotheses, including oxidative stress, central cholinergic system, neuroinflammation, neuronal apoptosis, synaptic plasticity.As chronic disease multifactorial etiology, combined therapy, targeting multiple pathophysiological factors, may be future trend VaD.

Language: Английский

Citations

60
Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: implications for neurodegenerative disorders DOI Creative Commons

Joanna K. Winstone,

Khyatiben V. Pathak, Wendy Winslow

et al.

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: July 28, 2022

Abstract Background Herbicides are environmental contaminants that have gained much attention due to the potential hazards they pose human health. Glyphosate, active ingredient in many commercial herbicides, is most heavily applied herbicide worldwide. The recent rise glyphosate application corn and soy crops correlates positively with increased death rates Alzheimer’s disease other neurodegenerative disorders. Glyphosate has been shown cross blood–brain barrier vitro models, but yet be verified vivo. Additionally, reports exposure increases pro-inflammatory cytokines blood plasma, particularly TNFα. Methods Here, we examined whether infiltrates brain elevates TNFα levels 4-month-old C57BL/6J mice. Mice received either 125, 250, or 500 mg/kg/day of glyphosate, a vehicle via oral gavage for 14 days. Urine, samples were collected on final day dosing analysis UPLC–MS ELISAs. Primary cortical neurons derived from amyloidogenic APP/PS1 pups evaluate changes Aβ 40-42 burden cytotoxicity. RNA sequencing was performed determine transcriptome. Results Our revealed infiltrated dose-dependent manner upregulated both plasma tissue post-exposure. Notably, measures correlated levels. primary soluble RNAseq over 200 differentially expressed genes cell-type-specific deconvolution showed enrichment key biological processes oligodendrocytes including myelination, axon ensheathment, glial cell development, oligodendrocyte development. Conclusions Collectively, these results show first time brain, expression Aβ, disrupts transcriptome manner, suggesting this may detrimental outcomes regarding health general population.

Language: Английский

Citations

49
Characterization of glyphosate-induced cardiovascular toxicity and apoptosis in zebrafish DOI
Jian Lu,

Weiguo Wang,

Cheng Zhang

et al.

The Science of The Total Environment, Journal Year: 2022, Volume and Issue: 851, P. 158308 - 158308

Published: Aug. 28, 2022

Language: Английский

Citations

49
Effects of glyphosate and glyphosate-based herbicides like Roundup™ on the mammalian nervous system: A review DOI
Najm Alsadat Madani, David O. Carpenter

Environmental Research, Journal Year: 2022, Volume and Issue: 214, P. 113933 - 113933

Published: July 19, 2022

Language: Английский

Citations

46
Glyphosate based-herbicide disrupts energy metabolism and activates inflammatory response through oxidative stress in mice liver DOI
Lei Qı, Yanmei Dong,

Hong Chao

et al.

Chemosphere, Journal Year: 2023, Volume and Issue: 315, P. 137751 - 137751

Published: Jan. 3, 2023

Language: Английский

Citations

26