Behavioral and dopaminergic damage induced by acute iron toxicity in Caenorhabditis elegans

Fagundez, Daiandra de Almeida; Câmara, Daniela De Freitas; Salgueiro, Willian G.; Noremberg, Simone; Puntel, Robson Luiz; Piccoli, Jacqueline Escobar; Garcia, Solange Cristina; Rocha, João Batista Teixeira da; Aschner, Michael; Ávila, Daiana Silva

doi:10.1039/c4tx00120f

Cited by 20 publications

(19 citation statements)

References 43 publications

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“…Piperazine designer drugs also altered the C. elegans reproductive process. Worms showed decreased egg laying after exposure to BZP, MeOPP and MDBP, which might indicate the late development of animal gonads, as demonstrated in other studies with metal compounds (Hu et al, ; Fagundez et al, ). The piperazine designer drugs effects are related to the effects induced by amphetamines, which, in C. elegans , are mediated by dopamine pathways (Carvelli, Matthies, & Galli, ).…”

Section: Discussionsupporting

confidence: 63%

“…In rats, BZP increased locomotor activity (Brennan et al, 2007;Yarosh et al, 2007), enhanced the acquisition and consolidation of memory and presented an anxiogenic profile (Castillo-Hernández et al, 2017), acting selectively at DAT and releasing dopamine (Simmler, Rickli, Schramm, Hoener, & Liechti, 2014). In C. elegans, when neuronal functions are impaired, changes in behavior may appear (Fagundez et al, 2015). The treated worms showed decreased motor function and reduced mechanical sensitivity, which strongly suggests that these drugs might induce neuronal damage.…”

Section: Discussionmentioning

confidence: 99%

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Piperazine designer drugs elicit toxicity in the alternative in vivo model Caenorhabditis elegans

Souto

Göethel

Peruzzi

et al. 2019

J of Applied Toxicology

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Piperazine designer drugs are a group of synthetic drugs of abuse that have appeared on the illicit market since the second half of the 1990s. The most common derivatives are 1‐benzylpiperazine (BZP), 1‐(4‐methoxyphenyl)piperazine (MeOPP) and 1‐(3,4‐methylenedioxybenzyl)piperazine (MDBP). They can be consumed as capsules, tablets, but also in powder or liquid forms. Generally, although less potent than amphetamines, piperazines have dopaminergic and serotonergic activities. The aim of this work was to evaluate the toxic effects of BZP, MeOPP and MDBP using Caenorhabditis elegans as in vivo model for acute toxicity, development, reproduction and behavior testing. The LC50 for BZP, MeOPP and MDBP were 52.21, 5.72 and 1.22 mm, respectively. All concentrations induced a significant decrease in the body surface of the worms, indicating developmental alterations, and decrease in the brood size. Worms exposed to piperazine designer drugs also presented a decrease in locomotor activity and mechanical sensitivity, suggesting the possible dysfunction of the nervous system. Neuronal damage was confirmed through the decrease in fluorescence of BY200 strains, indicating loss of dopaminergic transporters. In conclusion, we suggest that piperazine designer drugs lead to neuronal damage, which might be the underlying cause of the altered behavior observed in humans.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Piperazine designer drugs elicit toxicity in the alternative in vivo model Caenorhabditis elegans

Souto

Göethel

Peruzzi

et al. 2019

J of Applied Toxicology

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“…The survival rate of the mice was calculated as (number of live mice/ total number of mice tested)×100 %. The LD 50 values of the complexes were calculated according to the OECD guideline 425 . Animal assays were performed in compliance with the local ethnics committee.…”

Section: Methodsmentioning

confidence: 99%

“…The LD 50 values of the complexes were calculated according to the OECD guideline 425. [39] Animal assays were performed in compliance with the local ethnics committee.…”

Section: Acute Toxicitymentioning

confidence: 99%

Dinuclear Platinum(II) Complexes with Bone‐Targeting Groups as Potential Anti‐Osteosarcoma Agents

Zhang

Wang

Luo

et al. 2017

Chemistry An Asian Journal

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“…We induced mild oxidative stress in C. elegans by exposing animals (L4 stage) to low non-lethal Fe 2+ concentrations (1 h, 1mM). Fe 2+ is a classic inductor of reactive oxygen species (ROS) in multiple biological systems, including C. elegans (29). After one hour of recovery, animals were subsequently exposed to a stronger oxidative stress (3 mM Fe 2+ ).…”

Section: Exposure To Mild Environmental Stressors Increases Resistancmentioning

confidence: 99%

Acute-stress impairs cytoprotective mechanisms through neural inhibition of the insulin pathway

Veuthey

Florman

et al. 2018

Preprint

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Persistent activation of the "fight-or-flight" response accelerates aging and increases the susceptibility to disease. We show that repeated induction of the C. elegans flight response inhibits conserved cytoprotective mechanisms. This acute-stress response activates neurons that release tyramine, the invertebrate analog of adrenaline/noradrenaline. Tyramine stimulates the DAF-2/Insulin/IGF-1 pathway and precludes the nuclear translocation of the DAF-16/FOXO transcription factor through the activation of an adrenergic-like receptor TYRA-3 in the intestine. In contrast, environmental long-term stressors, such as heat or oxidative stress, reduce tyramine release allowing the induction of FOXO-dependent cytoprotective genes. These findings demonstrate how a neural stress-hormone signaling provides a statedependent neural switch between acute and long-term stress responses, and provide mechanistic insights how acute stress impairs cellular defensive systems. One Sentence Summary: The "fight-or-flight" response reduces resistance to environmental challenges.

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Behavioral and dopaminergic damage induced by acute iron toxicity in Caenorhabditis elegans

Abstract: Iron (Fe) exposure, results in multiple biological defects in C. elegans, including reproductive and motor impairment, which may be related to oxidative stress and neuronal damage.

Cited by 20 publications

References 43 publications

Piperazine designer drugs elicit toxicity in the alternative in vivo model Caenorhabditis elegans

Piperazine designer drugs elicit toxicity in the alternative in vivo model Caenorhabditis elegans

Dinuclear Platinum(II) Complexes with Bone‐Targeting Groups as Potential Anti‐Osteosarcoma Agents

Acute-stress impairs cytoprotective mechanisms through neural inhibition of the insulin pathway

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