Mini review. Cadmium neurotoxicity

Departamento de Neuropatología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Insurgentes Sur 3877, La Fama Tlalpan C.P. 14269, D.F., Mexico.
Environmental Toxicology and Pharmacology (Impact Factor: 2.08). 05/2007; 23(3):350-8. DOI: 10.1016/j.etap.2006.11.009
Source: PubMed


The Cd has been recognized as one of the most toxic environmental and industrial pollutants due to its ability to induce disturbances in several organs and tissues following either acute or chronic exposure. This review accounts for the recent evidence on its mechanisms to induce neurotoxicity, the role of the blood-brain barrier, oxidative stress, interference with calcium, and zinc-dependent processes and apoptosis induction as well as the modulatory effect of metallothionein. Discussion about cadmium neurotoxicity is centered on mechanisms of induction of cellular disfunctions. Future investigations must address those neuronal mechanisms in detail in order to understand cadmium-induced neurotoxicity.

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    • "Cadmium, a toxic environmental contaminant, can penetrate the blood–brain barrier, thereby causing CNS neurotoxicity following either acute or chronic exposure (Pihl and Parkes 1977; Wright et al. 2006; Wang and Du 2013). A growing number of studies have shown Cd's neurotoxicity as an etiological factor of neurodegenerative diseases including PD, AD, and ALS (Okuda et al. 1997; Panayi et al. 2002; Mendez-Armenta and Rios 2007; Goncalves et al. 2010). Therefore, finding a novel therapeutic strategy to prevent "
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    ABSTRACT: Cadmium (Cd), a toxic environmental contaminant, induces neurodegenerative disorders. Resveratrol, a natural product, has been found to exert neuroprotective effects. However, little is known regarding the effect of resveratrol on Cd-evoked neurotoxicity. Here we show that resveratrol effectively reversed Cd-elicited cell viability reduction, morphological change, nuclear fragmentation and condensation, as well as activation of caspase-3 in neuronal cells, implying neuroprotection against Cd-poisoning by resveratrol. Further research revealed that both c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases 1/2 (Erk1/2) were involved in the inhibitory effect of resveratrol on Cd-induced cell death, as selective inhibitors of Erk1/2 (U0126) and JNK (SP600125), or overexpression of dominant negative mitogen-activated protein kinase kinase 1 (MKK1) or dominant negative c-Jun potentiated resveratrol's prevention of Cd-induced phosphorylation of JNK and Erk1/2, as well as cell death in neuronal cells. Interestingly, resveratrol potently rescued the cells from Cd-induced suppression of protein phosphatases 2A (PP2A) and 5 (PP5) activity. Overexpression of PP2A or PP5 strengthened the inhibitory effects of resveratrol on Cd-induced activation of Erk1/2 and/or JNK, as well as cell death. The results indicate that resveratrol prevents Cd-induced activation of Erk1/2 and JNK pathways and neuronal cell death in part via activating PP2A and PP5. Our findings strongly support the notion that resveratrol may serve as a potential therapeutic agent in the prevention of Cd-induced neurodegenerative diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jul 2015 · Journal of Neurochemistry
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    • "Clinical and epidemiological data have shown that Cd exerts its toxic effects not only on the kidneys, liver and testis but also on the central nervous system (CNS) (Johri et al., 2010; Jomova and Valko, 2011; Mendez-Armenta and Rios, 2007; Okuda et al., 1997; Thompson and Bannigan, 2008). Cd can penetrate the bloodebrain barrier and accumulate in the brain, which contributes to the brain damage, and is thought to play a crucial role in human neurodegenerative diseases (Goncalves et al., 2010; Johnson, 2001; Mendez-Armenta and Rios, 2007; Okuda et al., 1997; Panayi et al., 2002; Watjen and Beyersmann, 2004). Therefore , it is of great importance to find a novel therapeutic target and strategy to control the neurotoxicity of Cd to brain. "
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    ABSTRACT: Cadmium (Cd), a toxic environmental contaminant, contributes to neurodegeneration. Rapamycin, a macrocyclic lactone, has shown preventive effect on Cd-induced neuronal cell death. However, the underlying mechanism is not fully understood. Here, we show that rapamycin prevented Cd-induced apoptotic cell death in neuronal cells. Coincidently, rapamycin markedly blocked Cd-induced phosphorylation of Akt, S6K1 and 4E-BP1 in the cells. Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of Cd-induced cell death, implying that the preventive effect of rapamycin on Cd-induced neurotoxicity is mTOR kinase activity-dependent. It appeared that both mTORC1 and mTORC2 were involved in the inhibitory activity of rapamycin, as silencing raptor, rictor or raptor/rictor enhanced rapamycin's blockage of Cd-induced cell death. Furthermore, downregulation of S6K1, ectopic expression of constitutively hypophosphorylated 4E-BP1 or dominant negative Akt, or co-treatment with Akt inhibitor also potentiated the rapamycin's inhibitory effect. The findings indicate that rapamycin prevents Cd-induced neuronal cell death via suppressing both mTORC1 and mTORC2 pathways. Our results highlight that rapamycin may be exploited for the prevention of Cd-induced neurodegenerative disorders. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · May 2015 · Neuropharmacology
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    • "Oxidative stress affects numerous cellular components, such as proteins, DNA and lipids through oxidation reactions . These alterations in structure produce significant changes in cellular function [70]. "
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    ABSTRACT: The present study investigated the effects of quercetin on the impairment of memory and anxiogenic - like behavior induced by cadmium (Cd) exposure. We also investigated possible alterations in acetylcholinesterase (AChE), Na(+),K(+)-ATPase and δ - aminolevulinate dehydratase (δ-ALA-D) activities as well as in oxidative stress parameters in the CNS. Rats were exposed to Cd (2.5mg/Kg) and quercetin (5, 25 or 50mg/Kg) by gavage for 45days. Animals were divided into eight groups (n=10-14): saline/control, saline/Querc 5mg/kg, saline/Querc 25mg/kg, saline/Querc 50mg/kg, Cd/ethanol, Cd/Querc 5mg/kg, Cd/Querc 25mg/kg and Cd/Querc 50mg/kg. Results demonstrated that Cd impaired memory and has anxiogenic effect.Quercetin prevented these harmful effects induced by Cd. AChE activity decreased in cerebral cortex and hippocampus and increased in hypothalamus of Cd-exposed rats. The Na(+),K(+)-ATPase activity decreased in cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin prevented these effects in AChE and Na(+),K(+)-ATPase activities. Reactive oxygen species production, thiobarbituric acid reactive substance levels, protein carbonyl content and double - stranded DNA fractions increased in cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin prevents totally or partially these effects caused by Cd. Total thiols (T-SH), reduced glutathione (GSH), reductase glutathione (GR) activities decreased and glutathione S-transferase (GST) activity increased Cd exposure rats. Co-treatment with quercetin prevented reduction in T-SH, GSH, GR activities and the rise of GST activity. The present findings show that quercetin prevents alterations in oxidative stress parameters as well as AChE and Na(+),K(+)-ATPase activities, consequently preventing memory impairment and anxiogenic-like behavior displayed by Cd exposure. These results may contribute to a better understanding of the neuroprotective role of quercetin, emphasizing the influence of this flavonoid in the diet for human health, possibly preventing brain injury associated with Cd intoxication.
    Full-text · Article · Jun 2014 · Physiology & Behavior
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