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

Abstract

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 contained GLY in formulation (fGLY) (0.065, 1.0 and 10.0 mg L fGLY) for 7 d, and an in vitro assay was performed using also pure GLY. Our results show that GBH induced in zebrafish brain a decrease in cell viability, inhibited mitochondrial complex enzymatic activity, modulated gene expression related to mitochondrial complexes, induced an increase in RS production, promoted hyperpolarization of mitochondrial membrane, and induced behavioral impairments. Together, our data contributes to the knowledge of the neurotoxic effects of GBH. Mitochondrial dysfunction has been recognized as a relevant cellular response that should not be disregarded. Moreover, this study pointed to the mitochondria as an important target of GBH.

Exposure to Sub-Acute Concentrations of Glyphosate Induce Clinico-Hematological, Serum Biochemical and Genotoxic Damage in Adult Cockerels

“…Among different herbicides, glyphosate (Nphosphonomethyl-glycine) is widely used herbicide across the globe to control unwanted weeds. It controls weeds via inhibition of a key enzyme (5enolpyruvylshikimate-3-phosphate synthase) responsible for synthesis of aromatic amino acids in plants (Pereira et al, 2018). The investigation of deleterious effects of widely used glyphosate is of vital importance as different reports have indicated the presence of its residue in food and water.…”

“…Glyphosate is one of the important members of broad spectrum herbicides and is frequently used in different cereal and food crops throughout the world to remove unwanted weeds (Pereira et al, 2018). For the last decade, the uses of herbicides have tremendously increased in vegetation control, agriculture and non-agricultural areas due to development of resistant of different crop varieties against glyphosate.…”

Bioactivity and Bactericidal Mechanism of Histidine-Rich β-Hairpin Peptide Against Gram-Negative Bacteria

“…However, PG-1 also has high cytotoxicity and hemolytic activity, which hinders its development as a candidate antimicrobial agent [11]. However, studies have shown that PG-1 might serve as a useful nontoxic stable scaffold for future therapeutic peptide analogs [12]. Previous work has shown that replacing lysine residues with histidine residues can reduce the cytotoxicity of histidine-containing peptides and that most of the peptides maintain excellent antibacterial activity [13].…”

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

“…Cholinergic neurons from the MS are highly sensible to oxidative stress (McKinney and Jacksonville, 2005). The mitochondrial toxicity induced by GlyBH (Bailey et al, 2018;Gomes and Juneau, 2016;Olorunsogo et al, 1979;Peixoto, 2005;Pereira et al, 2018) could affect the cholinergic neuron physiology, since mitochondrial dysfunction is involved in the beginning of neuronal deterioration (Guo et al, 2017;Lezi and Swerdlow, 2012). The alterations observed in the number of ChAT (+) cells in the MS together with the lower α7-nAChR expression in the HPC could contribute to the anxiogenic behaviour and the recognition memory impairments observed in intranasally GlyBH-treated mice (Baier et al, 2017).…”