Manganese toxicity upon overexposure.
Manganese (Mn) is a required element and a metabolic byproduct of the contrast agent mangafodipir trisodium (MnDPDP). The Mn released from MnDPDP is initially sequestered by the liver for first-pass elimination, which allows an enhanced contrast for diagnostic imaging. The administration of intravenous Mn impacts its homeostatic balance in the human body and can lead to toxicity. Human Mn deficiency has been reported in patients on parenteral nutrition and in micronutrient studies. Mn toxicity has been reported through occupational (e.g. welder) and dietary overexposure and is evidenced primarily in the central nervous system, although lung, cardiac, liver, reproductive and fetal toxicity have been noted. Mn neurotoxicity results from an accumulation of the metal in brain tissue and results in a progressive disorder of the extrapyramidal system which is similar to Parkinson's disease. In order for Mn to distribute from blood into brain tissue, it must cross either the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BCB). Brain import, with no evidence of export, would lead to brain Mn accumulation and neurotoxicity. The mechanism for the neurodegenerative damage specific to select brain regions is not clearly understood. Disturbances in iron homeostasis and the valence state of Mn have been implicated as key factors in contributing to Mn toxicity. Chelation therapy with EDTA and supplementation with levodopa are the current treatment options, which are mildly and transiently efficacious. In conclusion, repeated administration of Mn, or compounds that readily release Mn, may increase the risk of Mn-induced toxicity.
Crossgrove
Janelle
J
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
Zheng
Wei
W
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003287:Contrast Media / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004492:Edetic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006321:Heart / Q000187:drug effects; D006801:Humans; D008345:Manganese / Q000009:adverse effects* / Q000493:pharmacokinetics*; D020149:Manganese Poisoning / Q000209:etiology* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D003287:Contrast Media; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid