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.
"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 "
[Show abstract][Hide abstract] 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.
Journal of Neurochemistry 07/2015; 135(3). DOI:10.1111/jnc.13233 · 4.28 Impact Factor
"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. "
"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 . "
[Show abstract][Hide abstract] 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.
Emma Deas, Nunilo Cremades, Plamena R. Angelova, Marthe Ludtmann, Zhi Yao, Serene Chen, Mathew Horrocks, Blerida Banushi, Daniel Little, Michael Devine, Paul Gissen, David Klenerman, Christopher Dobson, Nicholas Wood, Sonia Gandhi, Andrey Y. Abramov,
A. Alt ntas, J. Martini, U. H. Mortensen, C. T. Workman,
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.