The absorbed Mn can be excreted via urine and bile.
The primary combustion products of MMT are Mn phosphate, Mn sulfate, and an Mn phosphate/sulfate mixture. The fifth identified intracellular pool of manganese is free Mn2+. Excretion of Mn through urine is minor. For example, the low fractional absorption of manganese from soy formula has been related to its relatively high phytate content. Absorption of Mn can be influenced by various dietary factors such as iron, calcium, phosphorus, phytate, and amino acids. Similar results were observed by Dorman etal. The propensity of manganese to undergo olfactory transport may contribute to changes in the sense of smell and other neurologic effects (Lucchini et al., 2012a). Cross et al.
Dorman et al. A small fraction enters the systemic circulation, where it may become oxidized to Mn3+ and bound to transferrin. Daily s.c. injection of 200mg/kg PAS for 2, 3, or 6weeks after Mn exposure reduced Mn levels in liver, spleen, heart, and pancreas by 2533%. Mn is more available from hay to cattle than from silage. Currently, there is limited information concerning the hormonal regulation of manganese metabolism. After entering the liver, manganese enters one of at least five metabolic pools. Of note, these studies used an animal model in which one nostril was occluded, thus restricting olfactory transport of manganese to the side of the rat brain ipsilateral to the patent nostril. Manganese neurotoxicity is associated with neurological changes in the basal ganglia and degeneration of GABAminergic neurons within the globus pallidus (Roth 2006). injection of manganese sulfate for 25days. Rats were then euthanized by exsanguinations and Mn concentrations in different tissues, blood, and brain were determined by neutron activation analysis. Jiang etal. Absorption of manganese is thought to occur throughout the small intestine. The main uses of Mn are in alloys, mainly with iron. Biological effects of metal, metal oxide, and carbon-based nanomaterials on the nervous system are increasingly of concern (Karmakar etal., 2014). administration of relatively high doses are required in acute cases. The unique relationship between the nasal cavity and the brain makes direct delivery of certain xenobiotics to the brain possible (Ali etal., 2010; Illum, 2004; Landis etal., 2012; Merkus and van den Berg, 2007; Sunderman, 2001; Wu etal., 2008). Initial olfactory transport studies relied on instillation of radiolabeled manganese chloride (54MnCl2) into the nasal cavity of freshwater pike and other animals (Tjlve et al., 1996). It should be noted that the interaction between manganese and iron can also affect the functions of some enzymes. Thanks to Christopher Lloyd of salt Lake City Utah for providing these excellent spectra of Mn54, recorded with a GS-USB-PRO and 2" x 2" CsI(Tl) detector (March 2019). Silica and carbon-based nanomaterials are also widely used. (2009) studied effects of PAS on Mn levels in body fluids and tissues in rats after daily i.p. That this in fact occurs is illustrated by the observation that following the addition of manganese to cells in culture, there can be sharp reductions in ferritin protein abundance, whereas there are increases in transferrin receptor abundance. (2012) also demonstrated that translocation of ZnO nanoparticles can also occur via olfactory transport in a Sprague-Dawley rat model. Olfactory transport of manganese also occurs following inhalation (Brenneman etal., 2000b). Manganese uptake by the liver has been reported to occur by a unidirectional, saturable process with the properties of passive mediated transport. Manganese was used in glass making in Egypt and this use was continued by Roman glassmakers (Sayre & Smith,1961) and through Venetian 14th-century glass (Mccray,1998) until modern times. Neurological symptoms reflect extrapyramidal motor dysfunction that resembles Parkinsons disease following chronic exposure (Roth 2006). Once entering the liver, manganese enters one of at least five metabolic pools. By continuing you agree to the use of cookies.
Lewis etal. C.L. Certain types of nanomaterials have been suspected to use the olfactory nerve pathway as a portal of entry into the mammalian brain.
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Manganese crosses synapses within the olfactory pathway and travels along secondary and tertiary neurons to more distal sites within the brain. A.; Robertson, I. D. Toxicol. PAS appears to be the most promising agent, although clinical experience is limited, and animal experiments indicate that i.v. In these studies, direct delivery along the olfactory route accounted for nearly all of the 54Mn found in the olfactory bulb and tract of the rat brain following acute manganese inhalation. Manganese absorption and retention are higher in neonates than in adults. Studies in vivo suggest that the Mn3+ complex forms very quickly in blood, in contrast to the slow oxidation of the Mn2+transferrin complex in vitro. At the subcellular level, Mn preferentially accumulates in mitochondria, where it disrupts oxidative phosphorylation and increases the generation of reactive oxygen species (ROS) (Gunter et al., 2006). Likewise, 30nm zinc oxide (ZnO) nanoparticles instilled in the rat nasal cavity the rat olfactory system resulted in injury to the olfactory epithelium and inflammation (Gao etal., 2013). She received 15 courses with the FDA-approved anti-tuberculosis drug PAS, 6g i.v. Tandon, Chandra, Singh, Husain, and Seth (1975) investigated structurally different chelating agents for ability to mobilize Mn from liver and testis of rats given i.p. If you for any reason you require a refund or replacement, please.
She had severe neuropathy with hand tremor, hypermyotonia, palpitations, and lower limb myalgia. Klaassen (1974) observed that rats excreted proportionately more Mn into bile than rabbits and dogs. Brain Kin values for any one of the three Mn species studied, i.e., 54Mn2+, 54Mn citrate, and 54Mn transferrin (54Mn-Tf), generally did not significantly differ among brain regions and the choroid plexus. Exposure concentrations were 3000, 300, and 30g Mn/m3. administration of these Mn compounds (once a week, 4weeks). A chelation schedule in chronic manganese poisoning (manganism) is not established, but DTPA, EDTA, and PAS are available as potential chelators. loss of smell (Lu, Huang, Chu, & Calne,1994), and their response to antiparkinson drugs such as L-dopa is only partial. Copyright 2022 Elsevier B.V. or its licensors or contributors. As such a route would bypass liver uptake and biliary excretion of Mn, its transport by the olfactory nerve directly to the brain might have toxicological importance (Fechter, 1999). D.C. Dorman, in Comprehensive Toxicology, 2010. Significant uptake of Mn by other brain regions was not observed until the third day, when the basal forebrain, cerebral cortex, hypothalamus, and striatum had 21%, 2%, 3%, and 1% of the measured label, respectively. Following ingestion, effectiveness of the gut in preventing excess absorption blunts the effect of biliary excretion (Abrams et al., 1977; Davis et al., 1993; Malecki et al., 1996). Manganese uptake by extrahepatic tissue does not seem to be increased under conditions of manganese deficiency, suggesting that manganese, in marked contrast to iron, does not play a role in the induction (or suppression) of manganese transport proteins. Cross etal. Dorman et al. (2005) reported that the rat trigeminal nerve may also absorb and deliver manganese from the nasal cavity to the brain. Studies in avians have demonstrated that high dietary phosphorus reduced manganese deposition in bone by approximately 50%. Another 14 isotopes have very short half-lives. Studies in avian species have demonstrated that high dietary phosphorus intakes decrease manganese deposition in bone by approximately 50%. Reproduced from Dorman, D. C.; Struve, M. F.; Wong, B. Mitrochondria have a large capacity for manganese uptake, and it is thought that mitochondrial uptake and release of manganese may be related. Tandon and Khandewal (1982a) studied effects of selected polyaminocarboxylic acids and thiol containing chelators on tissue distribution and urinary and fecal excretion of 54Mn in rats. Eybl, Sykora, and Mertl (1969) compared effects of various polyaminopolycarboxylic acids on the toxicokinetics of MnCl2 in the rat after injection of both chelator and Mn. Manganese entering the portal blood from the gastrointestinal tract may either remain free or become associated with 2-macroglobulin, which is subsequently taken up by the liver. Given that the average diet of many individuals may be considered marginal in manganese, and high in phosphorus, this antagonism may have important implications for human health. C.L. Manganese uptake by extrahepatic tissue does not appear to be increased under conditions of manganese deficiency, suggesting a lack of inducible manganese-transport proteins.
Other studies also showed that, when compared with adults, neonatal rodents attained higher brain Mn levels following similar oral exposures (Kontur and Fechter, 1985; Dorman et al., 2000). Henry (1995) estimated the relative bioavailability of Mn to poultry was 0.55 from manganese carbonate, 0.3 from manganese dioxide and 0.75 from manganese monoxide, when the bioavailability of manganese from manganese sulfate and manganese chloride was considered to be 1. After absorption from the gut, Mn is transported to the liver by 2-macroglobulins and albumin (Andersen et al., 1999). To date, the physicochemical properties and pharmacokinetic factors associated with olfactory transport remain poorly understood (Mistry etal., 2015).
injections of 6mg Mn/kg as MnCl2, 5days/week for 4weeks, which increased Mn levels in brain and soft tissues, plasma, red blood cells, and cerebrospinal fluid.
Initial studies examining direct nose-to-brain transport of manganese relied on intranasal instillation of radiolabeled manganese chloride (54MnCl2) and documented the presence of 54Mn in the olfactory bulb of rats, mice, and freshwater pike on the side ipsilateral to the instilled nostril (Tjlve and Henriksson, 1999). As Mn dioxide and other inhaled Mn compounds are practically insoluble in water, only Mn in particles small enough to reach the alveolar lining can be absorbed into the blood (WHO, 1981). ScienceDirect is a registered trademark of Elsevier B.V. ScienceDirect is a registered trademark of Elsevier B.V. Natural Resistance Associated Macrophage Protein 2, Hurley and Keen, 1987; Davis et al., 1993, Aschner et al., 1992; Sidoryk-Wegrzynowicz and Aschner, 2013, Chen et al., 2006a; Anderson et al., 2007, Kontur and Fechter, 1985; Dorman et al., 2000, Aschner and Aschner, 2005; Austinc et al., 2016, Abrams et al., 1977; Davis et al., 1993; Malecki et al., 1996, Encyclopedia of Human Nutrition (Third Edition), Encyclopedia of Food Sciences and Nutrition (Second Edition), DIETARY FIBER | Effects of Fiber on Absorption, Chelation Treatment During Acute and Chronic Metal OverexposuresExperimental and Clinical Studies, Chelation Therapy in the Treatment of Metal Intoxication, Tandon, Chandra, Singh, Husain, and Seth (1975), Ali etal., 2010; Illum, 2004; Landis etal., 2012; Merkus and van den Berg, 2007; Sunderman, 2001; Wu etal., 2008, Karmakar etal., 2014, Oberdrster etal., 2004, Environmental Factors in Neurodegenerative Diseases, Henriksson et al., 1999; Tjlve and Henriksson, 1999, Brenneman et al., 2000; Elder et al., 2006; Fechter et al., 2002, Handbook on the Toxicology of Metals (Fifth Edition), Brain barrier systems: a new frontier in metal neurotoxicological research. This tendency of neonates to attain higher brain Mn concentrations may reflect a less than optimal BBB, markedly reduced biliary Mn excretion rates, and/or increased placental Mn concentration (Aschner and Aschner, 2005; Austinc et al., 2016). The higher retention of manganese in young animals in relation to adults may reflect an immaturity of manganese excretory pathways. Polyaminocarboxylic acids with oxygen and nitrogen as ligands more effectively than sulfhydryl chelating agents prevented mortality after a lethal manganese chloride dose. Other studies in rats indicated that absorption via the olfactory mucosa is a potential contributor to brain Mn deposition. These changes were assessed post-exposure using a vanillin sniff test, MRI, and histologic approaches. At follow-up in 2004, 17years after the treatment, she had normal clinical and neurologic status and a normal brain magnetic resonance imaging. Based on the limited information available, chelating agents with O- and N-ligands seem to be effective in acute Mn poisoning. T1 MRI images collected from monkeys exposed for 90 days to either (a) air or (b) manganese sulfate at 1.5mgMnm3. (2006c) also used brain MRI and measurement of tissue manganese concentrations to demonstrate presumed olfactory transport of inhaled manganese sulfate in rhesus monkeys. For example, inhaled CdSe/ZnS nanocrystal quantum dots in mice anterogradely moved in the axons of the olfactory nerve to the olfactory bulbs (Hopkins etal., 2014). The arrow shows increased signal intensity in the olfactory bulb, a finding consistent with accumulation of manganese at this site. Although olfactory transport rapidly delivers manganese to brain structures in the olfactory pathway, it appears to be relatively slow (and perhaps inefficient) in delivering inhaled manganese to the rat striatum and other more distant brain structures. Absorption of Mn is via oral and inhalation routes. Following absorption, Mn can be distributed to many organs. There are no products to list in this category. Fluctuations in the free manganese pool may be an important regulator of cellular metabolic control in a manner analogous to those for free Ca2+ and Mg2+. Wei Zheng, Jean-Francois Ghersi-Egea, in Toxicology and Applied Pharmacology, 2003. Henriksson and Tjlve (2000) found that intranasal instillation of manganese results in alterations in olfactory bulb expression of glial fibrillary acidic protein (GFAP) and S-100b in rats. The authors also studied the distribution of Mn in blood, liver, and brain regions (cortex, cerebellum, striatum) following i.t. Manganese in the lung and in the olfactory bulb was dose dependent. Kao etal. Combined chelation was not more effective than the individual compounds. 2006, 92 (1), 219227. This process has been found to account for the clearance of a significant fraction of Mn-containing particles initially deposited in the lung (Drown etal., 1986; Newland etal., 1987). Similar MRI evidence of delivery of manganese to the olfactory bulb has also been seen in asymptomatic welders (Sen etal., 2011). The transport of Mn across the olfactory pathway is further demonstrated for the ultrafine particles, and this may result in the accumulation of Mn and inflammatory changes at the olfactory bulb to a greater extent than in the lung (Elder etal., 2006). Olfactory transport of manganese also occurs following inhalation (Brenneman et al. 2008). Return shipping address: Bee Research, Po Box 6259, Alexandria, NSW 2020, Australia, PRA - FREE Gamma Spectroscopy Software download, U.S. NRC Exempt Quantity Limit: 10 Ci (370 kBq), IAEA Exempt Quantity Limit: 27 Ci (1000 kBq). The low fractional absorption of manganese from soy formula has been related to its relatively high phytate content. 2004). per day for 4days, and 3days rest before the next course. These proteins are known markers of damage to astrocytes, important support cells found within the CNS. Absorption of Mn through the skin is negligible. Neuronal uptake may occur by passive diffusion, receptor-mediated uptake, or adsorptive endocytosis, followed by axonal transport, which takes several hours to days for manganese to reach the olfactory bulb and other regions of the central nervous system (CNS; Leavens et al., 2007). Her symptoms were significantly alleviated, and her handwriting improved. Wieczorek and Oberdrster (1989) gave seven daily i.p. In clinical studies chelation by EDTA in patients with chronic Mn poisoning, CaEDTA efficiently increased urinary Mn excretion. Manganese from manganese carbonate, dioxide and monoxide (relative bioavailabilities were 0.3, 0.35 and 0.6, respectively) was even less available to sheep than manganese sulfate (relative bioavailability was 1). Astocytes serve as the major homeostatic regulator and storage site for Mn in the brain (Aschner et al., 1992; Sidoryk-Wegrzynowicz and Aschner, 2013).
A small fraction enters the systemic circulation, where it may become oxidized to Mn3+ and bind to transferrin. Manganese uptake by the liver has been reported to occur by a unidirectional, saturable process with the properties of passive mediated transport. MnO2 is used as the cathode in alkaline and zinccarbon batteries. The past two decades has seen an explosion in our knowledge of manufactured nanomaterials (i.e., have at least one dimension in the range of 1100nm). Consistent with this concept, in pancreatic islets manganese blocks glucose-induced insulin release by altering cellular calcium fluxes, and manganese directly augments contractions in smooth muscle by a mechanism comparable to that of calcium. Data from balance studies indicate that manganese retention is very high during infancy, suggesting that neonates may be particularly susceptible to manganese toxicosis. Studies in-vivo suggest that the Mn3+ complex forms very quickly in blood, in contrast to the slow oxidation of Mn2+-transferrin complex in vitro. Furthermore, brain Mn concentrations are higher in developing animals, suggesting that high amounts of Mn are required for normal brain development in infants (Keen et al., 1986; Takeda et al., 1999). Furthermore, colored hair has higher Mn levels than noncolored hair. Animal studies on antidotal and decorporating effects of chelators in manganese poisoning are scarce.
Uptake and retention of dietary Mn was found to be greater in suckling than postweaning rats (Keen et al., 1986).
The 30,00024,000years old cave paintings in Gargas, Haute-Garonne were made with manganese pigments (Chalmin etal.,2006). The toxicological significance of olfactory transport of manganese remains controversial. A fourth manganese pool is incorporated into newly synthesized manganese proteins; biological half-lives for these proteins have not been agreed upon. Fluxes in the concentrations of adrenal, pancreatic, and pituitarygonadal axis hormones affect tissue manganese concentrations; however, it is not clear to what extent hormone-induced changes in tissue manganese concentrations are due to alterations in cellular uptake of manganese-activated enzymes or metalloenzymes.
The mechanisms by which manganese is transported to, and taken up by, extrahepatic tissues have not been identified. (1997) measured blood Mn levels in 3-month-old rats following intratracheal (i.t.) EDTA and DTPA were effective, DTPA more than EDTA. Multiple occupations are associated with the use of nanomaterials including workers in the automobile, aerospace, electronics and communications, and chemical and paint industries (Karmakar etal., 2014). (2006) who used MRI to observe increased manganese concentrations in the globus pallidus, putamen, olfactory epithelium, olfactory bulb, and cerebellum in rhesus monkeys exposed repeatedly to manganese sulfate at0.06mgMn/m3. Manganese neurotoxicity is most often associated with prolonged occupational exposure to abnormally high atmospheric concentrations of the metal. A.; Dye, J.
We use cookies to help provide and enhance our service and tailor content and ads. injections of CDTA or DTPA to rats starting immediately after inhalation exposure to a MnCl2 aerosol for 1h. Both chelators enhanced the urinary excretion of Mn extensively while the excretion was almost nil in the control group and in a group exposed to DMPS. Increased Mn concentrations were found in blood, kidney, lung, testes, and in all brain sections in the highest exposure group. Consistent with this idea, several studies in pancreatic islets have shown that manganese blocks glucose-induced insulin release by altering cellular calcium fluxes. Inhaled manganese can undergo dose-dependent direct nose-to-brain transport (Henriksson et al., 1999; Tjlve and Henriksson, 1999). The mechanisms underlying the interactions between iron and manganese have not been identified; however, they probably involve either a transport site or a ligand. At the end of the exposure period, locomotor activity and resting time tests were conducted for 36h using a computerized autotrack system. The largest producer is South Africa, possessing about 80% of known resources. Fluxes in the concentrations of adrenal, pancreatic, and pituitarygonadal axis hormones affect tissue manganese concentrations; however, it is not clear to what extent hormone-induced changes in tissue manganese concentrations are due to alterations in cellular uptake of manganese-activated enzymes or metalloenzymes.