Manganese accumulation in bone following chronic exposure in rats: Steady-state concentration and half-life in bone

O’Neal, Stefanie L.; Hong, Liping; Fu, Sherleen; Jiang, Wendy; Jones, Alexander Joseph; Nie, Linda H.; Zheng, Wei

doi:10.1016/j.toxlet.2014.06.019

Cited by 70 publications

(56 citation statements)

References 38 publications

(60 reference statements)

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“…was found to be relevant to bone Mn levels (65), indicating a possible redistribution of bone Mn to the central nervous system and a risk factor for developing manganism.…”

Section: Eliminationmentioning

confidence: 95%

“…In adult rats, atomic absorption spectrometry (AAS) revealed that Mn concentrations in bone reached a steady state after 6-week of Mn exposure, with approximately 2-3 fold increase of bone Mn levels before exposure (65). The half-life of Mn in femur, tibia and humerus bones was 77, 263 and 429 days, respectively; the average half-life of rat skeleton bone was 143 days, which was about 8.5. years in human (65). In addition, Mn concentrations in striatum, hippocampus and cerebrospinal fluid (CSF)…”

Section: Bonementioning

confidence: 99%

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Manganese metabolism in humans

2018

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Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER) stress, autophagy dysregulation, apoptosis, and disruption of other metal homeostasis. The mechanisms of Mn homeostasis are not fully understood. Here, we will address recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells. We will conclude with recommendations for future research areas on Mn metabolism.

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“…was found to be relevant to bone Mn levels (65), indicating a possible redistribution of bone Mn to the central nervous system and a risk factor for developing manganism.…”

Section: Eliminationmentioning

confidence: 95%

Section: Bonementioning

confidence: 99%

Manganese metabolism in humans

2018

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“…Mn accumulates predominantly in the bone; however, other organs such as the liver, kidneys, and the brain also store Mn [68–71]. Chronic exposure to Mn eventually leads to neurotoxicity and Parkinson disease-like symptoms [29, 63, 72–76].…”

Section: Optimal Mn Intake Range Is Relatively Narrowmentioning

confidence: 99%

Redox dynamics of manganese as a mitochondrial life-death switch

Smith

Fernandes

et al. 2017

Biochemical and Biophysical Research Communications

117

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Sten Orrenius, M.D., Ph.D., pioneered many areas of cellular and molecular toxicology and made seminal contributions to our knowledge of oxidative stress and glutathione (GSH) metabolism, organellar functions and Ca+2-dependent mechanisms of cell death, and mechanisms of apoptosis. On the occasion of his 80th birthday, we summarize current knowledge on redox biology of manganese (Mn) and its role in mechanisms of cell death. Mn is found in all organisms and has critical roles in cell survival and death mechanisms by regulating Mn-containing enzymes such as manganese superoxide dismutase (SOD2) or affecting expression and activity of caspases. Occupational exposures to Mn cause “manganism”, a Parkinson's disease-like condition of neurotoxicity, and experimental studies show that Mn exposure leads to accumulation of Mn in the brain, especially in mitochondria, and neuronal cell death occurs with features of an apoptotic mechanism. Interesting questions are why a ubiquitous metal that is essential for mitochondrial function would accumulate to excessive levels, cause increased H2O2 production and lead to cell death. Is this due to the interactions of Mn with other essential metals, such as iron, or with toxic metals, such as cadmium? Why is the Mn loading in the human brain so variable, and why is there such a narrow window between dietary adequacy and toxicity? Are non-neuronal tissues similarly vulnerable to insufficiency and excess, yet not characterized? We conclude that Mn is an important component of the redox interface between an organism and its environment and warrants detailed studies to understand the role of Mn as a mitochondrial life-death switch.

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“…Currently, there are no data reflecting the retention rate of Mn in human bone. In animal models, our recent study on a rat model suggests that the average half-life of Mn in rat bone is approximately 143 d for chronical oral exposure, which is equivalent to 8.5 years in human bone (O’Neal et al 2014). The data indicate that bone has a much longer half-life than other tissues.…”

Section: Introductionmentioning

confidence: 99%

Customized compact neutron activation analysis system to quantify manganese (Mn) in bonein vivo

et al. 2017

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Objective In the US alone, millions of workers, including over 300 000 welders, are at high risk of occupational manganese (Mn) exposure. Those who have been chronically exposed to excessive amount of Mn can develop severe neurological disorders similar, but not identical, to the idiopathic Parkinson’s disease. One challenge of identifing the health effects of Mn exposure is to find a reliable biomarker for exposure assessment, especially for long-term cumulative exposure. Approach Mn’s long biological half-life as well as its relatively high concentration in bone makes bone Mn (BnMn) a potentially valuable biomarker for Mn exposure. Our group has been working on the development of a deuterium–deuterium (D–D)-based neutron generator to quantify Mn in bone in vivo. Main results and significance In this paper, we report the latest advancements in our system. With a customized hand irradiation assembly, a fully characterized high purity germanium (HPGe) detector system, and an acceptable hand dose of 36 mSv, a detection limit of 0.64 µg Mn/g bone (ppm) has been achieved.

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Manganese accumulation in bone following chronic exposure in rats: Steady-state concentration and half-life in bone

Cited by 70 publications

References 38 publications

Manganese metabolism in humans

Manganese metabolism in humans

Redox dynamics of manganese as a mitochondrial life-death switch

Customized compact neutron activation analysis system to quantify manganese (Mn) in bonein vivo

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