| 毒性の概要 | Manganese is a metal required for numerous biochemical processes and its functions arise secondarily from its inclusion within protein structures as a cofactor. This includes for immune function and for the biochemical regulation of energy consumption, growth potential, coagulation, and hemostatic function. Also, manganese is involved with mechanisms to remove byproducts of aberrant oxidative stress. Plants are the main source of manganese in the diet. Other sources include vitamins, health products, drinking water that might contain trace amounts, and breast milk and formula for infants. Manganese toxicity, called manganism, is rare but might occur from occupational, accidental, and iatrogenic exposures. The main toxicity includes extra-pyramidal side-effects that closely resemble symptoms of Parkinson syndrome. This i secondary to deposition in specific components of the basal ganglia and the alteration of dopaminergic neuronal enzyme activity. Other noteworthy effects include cardiotoxicity, hepatotoxicity, and increased mortality in infants. Examples of exposures for the development of manganism include from chronic total parenteral nutrition (TPN) use in critically ill patients, the consumption of contaminated well-water, and exposure through welding, smelting, and mining. Manganese is readily absorbed through the intestinal tract, and absorption is variable based on the level of dietary intake, with biliary and pancreatic metabolism affecting excretion. However, these mechanisms are bypassed with IV administration, owing to the potentiality for manganism with IV preparations containing the essential metal.Manganese is a cellular toxicant that can impair transport systems, enzyme activities, and receptor functions. It primarily targets the central nervous system, particularily the globus pallidus of the basal ganglia. It is believed that the manganese ion, Mn(II), enhances the autoxidation or turnover of various intracellular catecholamines, leading to increased production of free radicals, reactive oxygen species, and other cytotoxic metabolites, along with a depletion of cellular antioxidant defense mechanisms, leading to oxidative damage and selective destruction of dopaminergic neurons. In addition to dopamine, manganese is thought to interact with other neurotransmitters, such as GABA and glutamate. Manganese overwhelms the manganese superoxide dismutase and produce oxidative damage. The neurotoxicity of Mn(II) has also been linked to its ability to substitute for Ca(II) under physiological conditions. It can enter mitochondria via the calcium uniporter and inhibit mitochondrial oxidative phosphorylation. It may also inhibit the efflux of Ca(II), which can result in a loss of mitochondrial membrane integrity. Mn(II) has been shown to inhibit mitochondrial aconitase activity to a significant level, altering amino acid metabolism and cellular iron homeostasis. (L228) |
|---|
