Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination

Abstract

This review attempts to summarize and clarify our basic knowledge as to the various factors that potentially influence the risks imposed from chronic exposure to high atmospheric levels of manganese (Mn). The studies describe the interrelationship of the different systems in the body that regulate Mn homeostasis by characterizing specific, biological components involved in its systemic and cellular uptake and its elimination from the body. A syndrome known as manganism occurs when individuals are exposed chronically to high levels of Mn, consisting of reduced response speed, intellectual deficits, mood changes, and compulsive behaviors in the initial stages of the disorder to more prominent and irreversible extrapyramidal dysfunction resembling Parkinson's disease upon protracted exposure. Mn intoxication is most often associated with occupations in which abnormally high atmospheric concentrations prevail, such as in welding and mining. There are three potentially important routes by which Mn in inspired air can gain access the body to: 1) direct uptake into the CNS via uptake into the olfactory or trigeminal presynaptic nerve endings located in the nasal mucosa and the subsequent retrograde axonal transport directly into the CNS; 2) transport across the pulmonary epithelial lining and its subsequent deposition into lymph or blood; and/or 3) mucocilliary elevator clearance from the lung and the subsequent ingestion of the metal in the gastrointestinal tract. Each of these processes and their overall contribution to the uptake of Mn in the body is discussed in this review as well as a description of the various mechanisms that have been proposed for the transport of Mn across the bloodbrain barrier which include both a transferrin-dependent and a transferrin-independent process that may involve store-operated Ca channels.

Contribution of metals to brain MR signal intensity: review articles

“…Manganese is present in food and water, but the intestine adjusts manganese absorption and only 1-5 % of the manganese ingested is absorbed [31]. In addition, the absorbed excess manganese is promptly excreted into the bile from the liver and rarely causes manganese toxicity [22,32]. Iron deficiency anemia promotes manganese absorption in the intestine and elevation of the manganese concentration in the blood, but the signal intensity of the globus pallidus on T1WI is not affected [33].…”

Manganese: A New Emerging Contaminant in the Environment

“…The manganese rates of accumulation, as well as its elimination, are relatively fast-regulated processes. The exposure to high levels of manganese causes toxicity and decreases the fitness of the organisms (Roth, 2006). In humans, the neurological damage induced by excessive manganese exposure has been well documented for over a century (Cooper, 1837;Mena et al, 1967;Normandin & Hazel, 2002;Takeda, 2003).…”

“…At the cellular level, manganese balance is proficiently managed by processes controlling cellular uptake, retention, and excretion (Roth, 2006), but these elaborate homeostatic mechanisms are altered under high levels of the available metal. Thus, it is important to consider that manganese dissolved in sea water is bio-concentrated significantly more at lower than at higher trophic levels (CICAD 63, 2004).…”

Safety and efficacy of manganese compounds (E5) as feed additives for all animal species: manganous carbonate; manganous chloride, tetrahydrate; manganous oxide; manganous sulphate, monohydrate; manganese chelate of amino acids, hydrate; manganese chelate of glycine, hydrate, based on a dossier submitted by FEFANA asbl

“…During the later stages of chronic toxicity, Parkinson-like symptoms such as tremor and muscle rigidity take place. Although manganism and true idiopathic Parkinson disease cause very similar deficits within the CNS, they differ in the neurotransmitters upon which they act; manganese toxicity results principally in the degeneration of γ-aminobutyric acid-ergic neurons in the globus pallidus whilst Parkinson disease is more associated with the dopaminergic neurons in the basal ganglia (Roth, 2006;cited by IEH, 2007).…”