Brain Manganese Deposition and Blood Levels in Patients Undergoing Home Parenteral Nutrition

Bertinet, D. Boggio; Tinivella, Marco; Balzola, F.; Francesco, Antonella De; Davini, Ottavio; Rizzo, Laura; Massarenti, Paola; Leonardi, Maria Antonietta; Balzola, F

doi:10.1177/0148607100024004223

Cited by 77 publications

(12 citation statements)

References 27 publications

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“…This factor combined with the high bioavailability of the metal in TPN increases the risk of Mn overload. That is also true for patients with hepatic dysfunction [17, 18, 21, 157]. …”

Section: Main Textmentioning

confidence: 99%

“…Patients with hepatic impairment and those receiving TPN, especially newborns, are susceptible to Mn accumulation [9, 17–19]. Infants and children are particularly vulnerable to inappropriate supplementation of Mn, which in some cases may lead to hypermanganesemia, dependent upon the duration of the treatment [17, 18, 20, 21]. Additionally, Mn is present at levels considered excessive in children’s formula [17].…”

Section: Introductionmentioning

confidence: 99%

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“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

Peres

Schettinger

Chen

et al. 2016

BMC Pharmacol Toxicol

283

183

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Manganese (Mn) is an essential heavy metal. However, Mn’s nutritional aspects are paralleled by its role as a neurotoxicant upon excessive exposure. In this review, we covered recent advances in identifying mechanisms of Mn uptake and its molecular actions in the brain as well as promising neuroprotective strategies. The authors focused on reporting findings regarding Mn transport mechanisms, Mn effects on cholinergic system, behavioral alterations induced by Mn exposure and studies of neuroprotective strategies against Mn intoxication. We report that exposure to Mn may arise from environmental sources, occupational settings, food, total parenteral nutrition (TPN), methcathinone drug abuse or even genetic factors, such as mutation in the transporter SLC30A10. Accumulation of Mn occurs mainly in the basal ganglia and leads to a syndrome called manganism, whose symptoms of cognitive dysfunction and motor impairment resemble Parkinson’s disease (PD). Various neurotransmitter systems may be impaired due to Mn, especially dopaminergic, but also cholinergic and GABAergic. Several proteins have been identified to transport Mn, including divalent metal tranporter-1 (DMT-1), SLC30A10, transferrin and ferroportin and allow its accumulation in the central nervous system. Parallel to identification of Mn neurotoxic properties, neuroprotective strategies have been reported, and these include endogenous antioxidants (for instance, vitamin E), plant extracts (complex mixtures containing polyphenols and non-characterized components), iron chelating agents, precursors of glutathione (GSH), and synthetic compounds that can experimentally afford protection against Mn-induced neurotoxicity.

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“…This factor combined with the high bioavailability of the metal in TPN increases the risk of Mn overload. That is also true for patients with hepatic dysfunction [17, 18, 21, 157]. …”

Section: Main Textmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

Peres

Schettinger

Chen

et al. 2016

BMC Pharmacol Toxicol

283

183

View full text Add to dashboard Cite

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“…Manganese is involved in a variety of reactions in processes involving immune function, bone and connective tissue development, reproductive function, neuronal health, and detoxification of free radicals [52]. As 90% is excreted in the bile [53], high levels can develop in PN patients with cholestasis, but elevated levels can be seen in patients with normal liver function as well [43,54,55]. In addition, it is possible that manganese can also contribute to cholestasis [56,57,58,59].…”

Section: Trace Elementsmentioning

confidence: 99%

Trace Elements in Parenteral Nutrition: Considerations for the Prescribing Clinician

2017

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Trace elements (TEs) are an essential component of parenteral nutrition (PN). Over the last few decades, there has been increased experience with PN, and with this knowledge more information about the management of trace elements has become available. There is increasing awareness of the effects of deficiencies and toxicities of certain trace elements. Despite this heightened awareness, much is still unknown in terms of trace element monitoring, the accuracy of different assays, and current TE contamination of solutions. The supplementation of TEs is a complex and important part of the PN prescription. Understanding the role of different disease states and the need for reduced or increased doses is essential. Given the heterogeneity of the PN patients, supplementation should be individualized.

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“…PD and Mn-induced parkinsonism share some similar cellular mechanisms including energy deficits, altered mitochondria function, protein aggregation, UPS dysfunction, and neurotoxic effects on dopamine neurons [69, 77]. Patients receiving total parenteral nutrition [78, 79] as well as those with chronic liver failure who are unable to efficiently excrete Mn in bile [80] are more likely to exhibit symptoms of Mn-induced parkinsonism. Despite the similarities in some of the shared pathophysiological mechanisms between PD and Mn-induced Parkinsonism, there are distinguishable features between the two disorders.…”

Section: Environmental Modulators In Pdmentioning

confidence: 99%

Disease-Toxicant Interactions in Parkinson’s Disease Neuropathology

2016

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Human disease commonly manifests as a result of complex genetic and environmental interactions. In the case of neurodegenerative diseases, such as Parkinson's disease (PD), understanding how environmental exposures collude with genetic polymorphisms in the central nervous system (CNS) to cause dysfunction is critical in order to develop better treatment strategies, therapies, and a more cohesive paradigm for future research. The intersection of genetics and the environment in disease etiology is particularly relevant in the context of their shared pathophysiological mechanisms. This review offers an integrated view of disease-toxicant interactions in PD. Particular attention is dedicated to how mutations in the genes SNCA, parkin, leucine-rich repeat kinase 2 (LRRK2) and DJ-1, as well as dysfunction of the ubiquitin proteasome system, may contribute to PD and how exposure to heavy metals, pesticides and illicit drugs may further the consequences of these mutations to exacerbate PD and PD-like disorders. Although the toxic effects induced by exposure to these environmental factors may not be the primary causes of PD, their mechanisms of action are critical for our current understanding of the neuropathologies driving PD. Elucidating how environment and genetics collude to cause pathogenesis of PD will facilitate the development of more effective treatments for the disease. Additionally, we discuss the neuroprotection exerted by estrogen and other compounds that may prevent PD and provide an overview of current treatment strategies and therapies.

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Brain Manganese Deposition and Blood Levels in Patients Undergoing Home Parenteral Nutrition

Cited by 77 publications

References 27 publications

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

Trace Elements in Parenteral Nutrition: Considerations for the Prescribing Clinician

Disease-Toxicant Interactions in Parkinson’s Disease Neuropathology

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