Neurotoxicity of glyphosate: Focus on molecular mechanisms probably associated with alterations in cognition and behavior

Chávez-Reyes, Jesús; Gutiérrez-Reyes, Cristian D.; Hernández-Cuellar, Eduardo; Marichal-Cancino, Bruno A.

doi:10.1016/j.etap.2024.104381

Cited by 7 publications

(4 citation statements)

References 82 publications

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“…It has recently been reported that GBH exerts metabolomic changes in rat serum for four important metabolites (i.e., paraxanthine, epinephrine, L-(+)-arginine, and D-arginine); these metabolites could be involved in neurological changes as proposed by an ingenuity pathway analysis [ 22 ]. It remains to be determined if some of those metabolomic alterations may explain the discrete alterations in cognition and behaviour induced by GBH exposition [ 7 ]. Also, some in vitro assays suggest that glyphosate is a weak inhibitor of the activity of cholinesterase, with inhibition ranges between 11.0 and 17.6% [ 8 , 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Even its use in other activities, such as gardening in residential areas, could contribute to possible urban exposure to glyphosate and AMPA [ 30 ]. In this sense, the negative effects of glyphosate on human health have been widely reported [ 7 ]; nevertheless, the potential toxicity of its metabolites must be considered.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, several reports have suggested multiple toxicological effects in preclinical and clinical studies [ 5 ]. Remarkably, some of these studies have reported teratogenic effects in the most dramatic cases [ 6 ], but also discrete alterations in cognition and behaviour [ 7 ], probably by a negative interaction with the enzyme acetylcholinesterase (AChE) [ 8 ]. In this regard, it has been shown that subchronic and chronic exposure to glyphosate decreased the activity of AChE in brain samples of rodents [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Aminomethylphosphonic Acid (AMPA), a Glyphosate Metabolite, Decreases Plasma Cholinesterase Activity in Rats

Chávez-Reyes,

Saráchaga-Terrazas,

Colis-Arenas

et al. 2024

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Glyphosate, a widely used herbicide, is linked to a plethora of deleterious effects in both clinical and preclinical studies. Nevertheless, the effects of its main metabolite, aminomethylphosphonic acid (AMPA), whose half-life in soil is even longer than that of glyphosate, have been little explored. On this basis, as a first approach, in this work, we report that intraperitoneal (i.p.) administration of AMPA or glyphosate (at 10, 56, and 100 mg/kg) decreased, to a similar extent, plasma cholinesterase (ChE) activity in acutely exposed rats. Moreover, we designed an experimental protocol to analyze and compare the effects of AMPA and glyphosate on human plasma ChE activity; this protocol consisted of adding these compounds to human plasma to subsequently test the effects of this plasma on the contraction to acetylcholine (ACh) in the frog rectus abdominis muscle (an indirect estimate of ChE activity). Accordingly, this muscular contraction to ACh was evaluated before and after pre-incubation of ACh with (i) plasma alone, (ii) plasma with AMPA, and (iii) plasma with glyphosate. Our results indicate that AMPA, like glyphosate, decreased ChE activity in the plasma of rats (when given i.p.) and humans (when added in vitro), suggesting that both xenobiotics may exert similar toxicological effects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aminomethylphosphonic Acid (AMPA), a Glyphosate Metabolite, Decreases Plasma Cholinesterase Activity in Rats

Chávez-Reyes,

Saráchaga-Terrazas,

Colis-Arenas

et al. 2024

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“…It was initially conceived that glyphosate is nontoxic to higher mammals, probably due to lack of shikimate enzymatic pathway in mammals, hence production of no physiological role [ 4 ]. Even though there is no related physiological role of shikimate pathway in mammals, there have been controversies on the potential health risks of chronic exposure to glyphosate from occupation, water, food, and environmental contamination [ 5 , 6 ]. However, glyphosate exposure has been implicated in the pathogenesis of several neurological disorders through stimulation of oxidative and inflammatory pathways [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Tannic acid inhibits pain mediators, inflammation and oxidative stress in mice exposed to glyphosate-based herbicide

Abolarin,

Owoyele

2024

Environ Anal Health Toxicol

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Chronic exposure to glyphosate-based herbicide (Gly) has been associated with neurological disorders. Tannic acid (TA) is an antioxidant with attenuating action against neuroinflammation-associated conditions. This study evaluated the effect of Gly on pain perception alongside antinociceptive and anti-inflammatory actions of TA in Gly-exposed mice. Male Swiss mice were randomly divided into six groups (n=8): control (distilled water 0.2 ml/kg), Gly (Gly 500 mg/kg), Pre-TA + Gly (TA 50 mg/kg pre-treatment, afterwards Gly-administered), TA + Gly (TA 50 mg/kg and Gly co-administered), Pre-AA + Gly (ascorbic acid (AA) 10 mg/kg pre-treatment, afterwards Gly-administered), and AA + Gly (AA 10 mg/kg and Gly co-administered). Mechanical, thermal, and chemical pain were evaluated six weeks post vehicle/drugs administrations orally, followed by brain biochemical measurements. TA treatment alleviated Gly-induced hyperalgesia in similar version to the values of control and AA groups by increasing significantly (p < 0.05) nociceptive thresholds. Moreover, TA-treatment significantly decreased malondialdehyde (MDA) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) levels, significantly increased anti-inflammatory cytokines (IL-10, IL-4, and TGF-1β) levels, and antioxidant enzymes, catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities compared to Gly-treated mice (p < 0.05). Conclusively, TA treatment exerted antinociceptive and anti-inflammatory actions, possibly through its antioxidant and anti-inflammatory actions in Gly-exposed mice. Notably, TA pre-treatment showed a better response than TA and Gly co-administration. We propose the potential neuroprotective and ameliorative functions of TA in Gly-induced hyperalgesia. This merits further clinical research into protective roles of TA against pesticide-related conditions.

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Acute glyphosate and aminomethylphosphonic acid (AMPA), its major metabolite, impaired spatial orientation, navigation, learning and/or memory in female rats

Chávez-Reyes,

López-Lariz,

Acosta-Cruz

et al. 2025

Behavioural Brain Research

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Neurotoxicity of glyphosate: Focus on molecular mechanisms probably associated with alterations in cognition and behavior

Cited by 7 publications

References 82 publications

Aminomethylphosphonic Acid (AMPA), a Glyphosate Metabolite, Decreases Plasma Cholinesterase Activity in Rats

Aminomethylphosphonic Acid (AMPA), a Glyphosate Metabolite, Decreases Plasma Cholinesterase Activity in Rats

Tannic acid inhibits pain mediators, inflammation and oxidative stress in mice exposed to glyphosate-based herbicide

Acute glyphosate and aminomethylphosphonic acid (AMPA), its major metabolite, impaired spatial orientation, navigation, learning and/or memory in female rats

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