Glyphosate-based herbicide impairs energy metabolism and increases autophagy in C6 astroglioma cell line (original) (raw)

Low-concentration exposure to glyphosate-based herbicide modulates the complexes of the mitochondrial respiratory chain and induces mitochondrial hyperpolarization in the Danio rerio brain

Chemosphere, 2018

Glyphosate (N-phosphonomethyl-glycine) (GLY) is the active ingredient of the most used herbicides in the world. GLY is applied in formulated products known as glyphosate-based herbicides (GBH), which could induce effects that are not predicted by toxicity assays with pure GLY. This herbicide is classified as organophosphorus compound, which is known to induce neurotoxic effects. Although this compound is classified as non-neurotoxic by regulatory agencies, acute exposure to GBH causes neurological symptoms in humans. However, there is no consensus in relation to neurotoxic effects of GBH. Thus, the aim of this study was to investigate the neurotoxic effects of the GBH in the zebrafish Danio rerio, focusing on acute toxicity, the activity and transcript levels of mitochondrial respiratory chain complexes, mitochondrial membrane potential, reactive species (RS) formation, and behavioral repertoire. Adult zebrafish were exposed in vivo to three concentrations of GBH Scout, which contai...

Intranasal Glyphosate-Based Herbicide Administration Alters the Redox Balance and the Cholinergic System in the Mouse Brain

2019

Pesticide exposure is associated with cognitive and psychomotor disorders. Glyphosate-based herbicides (GlyBH) are among the most used agrochemicals, and inhalation of GlyBH sprays may arise from frequent aerial pulverizations. Previously, we described that intranasal (IN) administration of GlyBH in mice decreases locomotor activity, increases anxiety, and impairs recognition memory. Then, the aim of the present study was to investigate the mechanisms involved in GlyBH neurotoxicity after IN administration. Adult male CF-1 mice were exposed to GlyBH IN administration (equivalent to 50 mg/kg/day of Gly acid, 3 days a week, during 4 weeks). Total thiol content and the activity of the enzymes catalase, acetylcholinesterase and transaminases were evaluated in different brain areas. In addition, markers of the cholinergic and the nigrostriatal pathways, as well as of astrocytes were evaluated by fluorescence microscopy in coronal brain sections. The brain areas chosen for analysis were t...

Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways

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

Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity

Toxicology, 2014

Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup ® (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30 min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup ® (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup ® (0.00005-0.1%) during 30 min and experiments were carried out to determine whether glyphosate affects 45 Ca 2+ influx and cell viability. Moreover, we investigated the pesticide effects on oxidative stress parameters, 14 C-␣-methyl-amino-isobutyric acid (14 C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup ® (30 min) increases 45 Ca 2+ influx by activating NMDA receptors and voltagedependent Ca 2+ channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup ®-induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup ® increased 3 H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. We also observed that both acute and chronic exposure to Roundup ® decreased 3 H-glutamate uptake and metabolism, while induced 45 Ca 2+ uptake and 14 C-MeAIB accumulation in immature rat hippocampus. Taken together, these results demonstrated that Roundup ® might lead to excessive extracellular glutamate levels and consequently to glutamate excitotoxicity and oxidative stress in rat hippocampus.

Toxicity of Neurons Treated with Herbicides and Neuroprotection by Mitochondria-Targeted Antioxidant SS31

International Journal of Environmental Research and Public Health, 2011

The purpose of this study was to determine the neurotoxicity of two commonly used herbicides: picloram and triclopyr and the neuroprotective effects of the mitochondria-targeted antioxidant, SS31. Using mouse neuroblastoma (N2a) cells and primary neurons from C57BL/6 mice, we investigated the toxicity of these herbicides, and protective effects of SS1 peptide against picloram and triclopyr toxicity. We measured total RNA content, cell viability and mRNA expression of peroxiredoxins, neuroprotective genes, mitochondrial-encoded electron transport chain (ETC) genes in N2a cells treated with herbicides and SS31. Using primary neurons from C57BL/6 mice, neuronal survival was studied in neurons treated with herbicides, in neurons pretreated with SS31 plus treated with herbicides, neurons treated with SS31 alone, and untreated neurons. Significantly decreased total RNA content, and cell viability in N2a cells treated with picloram and triclopyr were found compared to untreated N2a cells. Decreased mRNA

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...

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...