Wnt1 silencing enhances neurotoxicity induced by paraquat and maneb in SH‑SY5Y cells

Huang, Chen; Ma, Jing; Li, Baixiang; Sun, Yuena

doi:10.3892/etm.2019.7963

Cited by 6 publications

(7 citation statements)

References 45 publications

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“…Paraquat is considered as a substance inducing Parkinson’s-like pathology in animals and therefore is also used for modeling this pathology in monoaminergic cell culture (such as neuroblastoma SH-SY5Y or pheochromacytoma PC-12 [ 55 , 56 , 57 ]). Monoamine metabolism is very sensitive to oxidative stress produced by paraquat through dopamine quinone production, affecting mitochondrial function and protein folding [ 58 , 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

First Insight into the Neuroprotective and Antibacterial Effects of Phlorotannins Isolated from the Cell Walls of Brown Algae Fucus vesiculosus and Pelvetia canaliculata

et al. 2023

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Phaeophyceae (brown algae) essentially contribute to biotopes of cold and temperate seas. Their thalli are rich in biologically active natural products, which are strongly and universally dominated with phlorotannins—polyphenols of complex and diverse structure based on multiple differently arranged phloroglucinol units and well known as strong antioxidants with a broad spectrum of biological activities. In the algal cells, phlorotannins can either accumulate in the cytoplasm or can be secreted into the cell wall (CW). The biological activities of extractable intracellular phlorotannins have been comprehensively characterized, whereas the properties of the CW-bound polyphenol fraction are still mostly unknown. Recently, we identified dibenzodioxin bonding as the principal structural feature of the CW-bound phlorotannins in fucoid algae, whereas soluble intracellular phlorotannins rely on aryl and ether bonds. However, profiles of biological activity associated with these structural differences are still unknown. Therefore, to the best of our knowledge, for the first time we address the antioxidant, cytotoxic, neuroprotective, and antibacterial properties of the CW-bound phlorotannin fractions isolated from two representatives of the order Fucales—Fucus vesiculosus and Pelvetia canaliculata. The CW-bound phlorotannins appeared to be softer antioxidants, stronger antibacterial agents and were featured with essentially less cytotoxicity in comparison to the intracellular fraction. However, the neuroprotective effects of both sub-cellular phlorotannin fractions of F. vesiculosus and P. canaliculata were similar. Thus, due to their lower cytotoxicity, CW-bound phlorotannins can be considered as promising antioxidants and neuroprotectors.

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Section: Discussionmentioning

confidence: 99%

First Insight into the Neuroprotective and Antibacterial Effects of Phlorotannins Isolated from the Cell Walls of Brown Algae Fucus vesiculosus and Pelvetia canaliculata

et al. 2023

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“…Desde el punto de vista molecular, la neurotoxicidad del paraquat se explica por alteración en la expresión de señalizadores como Wnt1, Wnt5a o tirosina hidroxilasa, entre otros, que llevan a cambios en la proliferación y diferenciación de neuronas dopaminérgicas mesencefálicas. En modelos animales, en donde se induce daño neuronal del locus coeruleus y agotamiento de noradrenalina, inducido por paraquat y maneb, se descubrió que la N-etil-2-bromobecilamina (DSP-4) aumenta la neurodegeneración del hipocampo y produce activación microglial, que llevan a inflamación y a las consecuencias neurológicas de la intoxicación 24,25 .…”

Section: Discussionunclassified

Intoxicación por paraquat y convulsiones: a propósito de un caso en una institución de salud de Pasto, Nariño

Ordóñez

Zarama

2020

MedUPB

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Caso clínico de un hombre de 20 años, procedente de área rural de un municipio de Nariño, que consulta a un centro de salud después de 36 horas de haber ingerido de modo no intencional 20-30 mL de gramoxone (dicloruro de paraquat) mientras estaba en estado de embriaguez, con síntomas digestivos, hiperbilirrubinemia, elevación de azoados, leucocitosis y neutrofilia, por lo que es referido a un hospital de alta complejidad en la ciudad de Pasto. Durante su hospitalización, presenta epistaxis, falla renal con requerimiento de hemodiálisis, quemaduras orales, hipertermia y dos episodios de crisis convulsivas tónico-clónico generalizadas. Se toman paraclínicos: azoados, gases arteriales, electrolitos, glicemia, entre otros, cuyos resultados se enmarcan dentro de la normalidad durante los episodios convulsivos. Es relevante proporcionar elementos para construir un criterio clínico que explique el compromiso neurológico, ya que, es raro y complejo en intoxicaciones por herbicidas como el paraquat.

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“…The dopaminergic neuronal loss requires repeated chronic exposure to a low dose of paraquat to increase the reactive oxygen species production in the brain as well as to activate microglia 60 , 61 , 63 – 65 . Exposure to paraquat has been found to promote tyrosine phosphorylation of parkin and to silence Wnt/Wingless signalling in the dopaminergic SH-SY5Y cell line 66 , 67 . In addition, paraquat induces histone H3 acetylation and apoptosis in an in vitro model of PD 68 .…”

Section: Animal Studiesmentioning

confidence: 99%

Towards improved screening of toxins for Parkinson’s risk

Shan,

Heusinkveld,

Paul

et al. 2023

npj Parkinsons Dis.

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Parkinson’s disease (PD) is a chronic, progressive and disabling neurodegenerative disorder. The prevalence of PD has risen considerably over the past decades. A growing body of evidence suggest that exposure to environmental toxins, including pesticides, solvents and heavy metals (collectively called toxins), is at least in part responsible for this rapid growth. It is worrying that the current screening procedures being applied internationally to test for possible neurotoxicity of specific compounds offer inadequate insights into the risk of developing PD in humans. Improved screening procedures are therefore urgently needed. Our review first substantiates current evidence on the relation between exposure to environmental toxins and the risk of developing PD. We subsequently propose to replace the current standard toxin screening by a well-controlled multi-tier toxin screening involving the following steps: in silico studies (tier 1) followed by in vitro tests (tier 2), aiming to prioritize agents with human relevant routes of exposure. More in depth studies can be undertaken in tier 3, with whole-organism (in)vertebrate models. Tier 4 has a dedicated focus on cell loss in the substantia nigra and on the presumed mechanisms of neurotoxicity in rodent models, which are required to confirm or refute the possible neurotoxicity of any individual compound. This improved screening procedure should not only evaluate new pesticides that seek access to the market, but also critically assess all pesticides that are being used today, acknowledging that none of these has ever been proven to be safe from a perspective of PD. Importantly, the improved screening procedures should not just assess the neurotoxic risk of isolated compounds, but should also specifically look at the cumulative risk conveyed by exposure to commonly used combinations of pesticides (cocktails). The worldwide implementation of such an improved screening procedure, would be an essential step for policy makers and governments to recognize PD-related environmental risk factors.

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Wnt1 silencing enhances neurotoxicity induced by paraquat and maneb in SH‑SY5Y cells

Cited by 6 publications

References 45 publications

First Insight into the Neuroprotective and Antibacterial Effects of Phlorotannins Isolated from the Cell Walls of Brown Algae Fucus vesiculosus and Pelvetia canaliculata

First Insight into the Neuroprotective and Antibacterial Effects of Phlorotannins Isolated from the Cell Walls of Brown Algae Fucus vesiculosus and Pelvetia canaliculata

Intoxicación por paraquat y convulsiones: a propósito de un caso en una institución de salud de Pasto, Nariño

Towards improved screening of toxins for Parkinson’s risk

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