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Perinatal manganese exposure and hydroxyl radical formation in rat brain.

Bałasz M, Szkilnik R, Brus R, Malinowska-Borowska J, Kasperczyk S, Nowak D, Kostrzewa RM, Nowak P - Neurotox Res (2014)

Bottom Line: We found that Mn content in the brain, kidney, liver, and bone was significantly elevated in dams exposed to Mn during pregnancy.Also, damage to the dopaminergic system acts as a "trigger mechanism," initiating a cascade of adverse events leading to a protracted increase in HO(•) generation, and the effects of Mn and 6-OHDA are compounded.In conclusion, ontogenetic Mn exposure, resulting in reactive oxygen species, HO(•) formation, represents a risk factor for dopaminergic neurotoxicity and development of neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Toxicology and Occupational Health Protection, Public Health Faculty, Medical University of Silesia, Medykow 18, 40-752, Katowice Ligota, Poland.

ABSTRACT
The present study was designed to investigate the role of pre- and postnatal manganese (Mn) exposure on hydroxyl radical (HO(•)) formation in the brains of dopamine (DA) partially denervated rats (Parkinsonian rats). Wistar rats were given tap water containing 10,000 ppm manganese chloride during the duration of pregnancy and until the time of weaning. Control rat dams consumed tap water without added Mn. Three days after birth, rats of both groups were treated with 6-hydroxydopamine at one of three doses (15, 30, or 67 µg, intraventricular on each side), or saline vehicle. We found that Mn content in the brain, kidney, liver, and bone was significantly elevated in dams exposed to Mn during pregnancy. In neonates, the major organs that accumulated Mn were the femoral bone and liver. However, Mn was not elevated in tissues in adulthood. To determine the possible effect on generation of the reactive species, HO(•) in Mn-induced neurotoxicity, we analyzed the contents of 2.3- and 2.5-dihydroxybenzoic acid (spin trap products of salicylate; HO(•) being an index of in vivo HO(•) generation), as well as antioxidant enzyme activities of superoxide dismutase (SOD) isoenzymes and glutathione S-transferase (GST). 6-OHDA-depletion of DA produced enhanced HO(•) formation in the brain tissue of newborn and adulthood rats that had been exposed to Mn, and the latter effect did not depend on the extent of DA denervation. Additionally, the extraneuronal, microdialysate, content of HO(•) in neostriatum was likewise elevated in 6-OHDA-lesioned rats. Interestingly, there was no difference in extraneuronal HO(•) formation in the neostriatum of Mn-exposed versus control rats. In summary, findings in this study indicate that Mn crosses the placenta but in contrast to other heavy metals, Mn is not deposited long term in tissues. Also, damage to the dopaminergic system acts as a "trigger mechanism," initiating a cascade of adverse events leading to a protracted increase in HO(•) generation, and the effects of Mn and 6-OHDA are compounded. Moreover, HO(•) generation parallels the suppression of SOD isoenzymes and GST in the brains of rats lesioned with 6-OHDA and/or intoxicated with Mn-the most prominent impairments being in frontal cortex, striatum, and brain stem. In conclusion, ontogenetic Mn exposure, resulting in reactive oxygen species, HO(•) formation, represents a risk factor for dopaminergic neurotoxicity and development of neurodegenerative disorders.

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Tissue- and organ-specific manganese content in 8-week-old rats exposed to this metal (10,000 ppm) during pre- and perinatal development (n = 6). Legend is the same as in Fig. 1
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Fig5: Tissue- and organ-specific manganese content in 8-week-old rats exposed to this metal (10,000 ppm) during pre- and perinatal development (n = 6). Legend is the same as in Fig. 1

Mentions: Mn content in the frontal cortex, hippocampus, and neostriatum was significantly elevated in dams exposed to this metal during pregnancy and until weaning of pups, as compared to control rats [Fig. 1]. Additionally, significant elevations in Mn concentration were observed in the kidney, liver, and bone. Conversely, the Mn content in the femoral muscle and heart muscle was in the range of the respective control values [Fig. 2]. The primary organs showing accumulation of Mn in P14 pups from Mn-exposed mothers were the femoral bones and liver. Interestingly, there were no significant changes in Mn concentration in the brain, kidney, femoral bone, or heart muscle of P14 Mn-exposed pups [Fig. 3]. In 8-week-old rats, the concentration of Mn in all examined tissues was comparable between control and Mn-exposed rats [Figs. 4, 5].Fig. 1


Perinatal manganese exposure and hydroxyl radical formation in rat brain.

Bałasz M, Szkilnik R, Brus R, Malinowska-Borowska J, Kasperczyk S, Nowak D, Kostrzewa RM, Nowak P - Neurotox Res (2014)

Tissue- and organ-specific manganese content in 8-week-old rats exposed to this metal (10,000 ppm) during pre- and perinatal development (n = 6). Legend is the same as in Fig. 1
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4286139&req=5

Fig5: Tissue- and organ-specific manganese content in 8-week-old rats exposed to this metal (10,000 ppm) during pre- and perinatal development (n = 6). Legend is the same as in Fig. 1
Mentions: Mn content in the frontal cortex, hippocampus, and neostriatum was significantly elevated in dams exposed to this metal during pregnancy and until weaning of pups, as compared to control rats [Fig. 1]. Additionally, significant elevations in Mn concentration were observed in the kidney, liver, and bone. Conversely, the Mn content in the femoral muscle and heart muscle was in the range of the respective control values [Fig. 2]. The primary organs showing accumulation of Mn in P14 pups from Mn-exposed mothers were the femoral bones and liver. Interestingly, there were no significant changes in Mn concentration in the brain, kidney, femoral bone, or heart muscle of P14 Mn-exposed pups [Fig. 3]. In 8-week-old rats, the concentration of Mn in all examined tissues was comparable between control and Mn-exposed rats [Figs. 4, 5].Fig. 1

Bottom Line: We found that Mn content in the brain, kidney, liver, and bone was significantly elevated in dams exposed to Mn during pregnancy.Also, damage to the dopaminergic system acts as a "trigger mechanism," initiating a cascade of adverse events leading to a protracted increase in HO(•) generation, and the effects of Mn and 6-OHDA are compounded.In conclusion, ontogenetic Mn exposure, resulting in reactive oxygen species, HO(•) formation, represents a risk factor for dopaminergic neurotoxicity and development of neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Toxicology and Occupational Health Protection, Public Health Faculty, Medical University of Silesia, Medykow 18, 40-752, Katowice Ligota, Poland.

ABSTRACT
The present study was designed to investigate the role of pre- and postnatal manganese (Mn) exposure on hydroxyl radical (HO(•)) formation in the brains of dopamine (DA) partially denervated rats (Parkinsonian rats). Wistar rats were given tap water containing 10,000 ppm manganese chloride during the duration of pregnancy and until the time of weaning. Control rat dams consumed tap water without added Mn. Three days after birth, rats of both groups were treated with 6-hydroxydopamine at one of three doses (15, 30, or 67 µg, intraventricular on each side), or saline vehicle. We found that Mn content in the brain, kidney, liver, and bone was significantly elevated in dams exposed to Mn during pregnancy. In neonates, the major organs that accumulated Mn were the femoral bone and liver. However, Mn was not elevated in tissues in adulthood. To determine the possible effect on generation of the reactive species, HO(•) in Mn-induced neurotoxicity, we analyzed the contents of 2.3- and 2.5-dihydroxybenzoic acid (spin trap products of salicylate; HO(•) being an index of in vivo HO(•) generation), as well as antioxidant enzyme activities of superoxide dismutase (SOD) isoenzymes and glutathione S-transferase (GST). 6-OHDA-depletion of DA produced enhanced HO(•) formation in the brain tissue of newborn and adulthood rats that had been exposed to Mn, and the latter effect did not depend on the extent of DA denervation. Additionally, the extraneuronal, microdialysate, content of HO(•) in neostriatum was likewise elevated in 6-OHDA-lesioned rats. Interestingly, there was no difference in extraneuronal HO(•) formation in the neostriatum of Mn-exposed versus control rats. In summary, findings in this study indicate that Mn crosses the placenta but in contrast to other heavy metals, Mn is not deposited long term in tissues. Also, damage to the dopaminergic system acts as a "trigger mechanism," initiating a cascade of adverse events leading to a protracted increase in HO(•) generation, and the effects of Mn and 6-OHDA are compounded. Moreover, HO(•) generation parallels the suppression of SOD isoenzymes and GST in the brains of rats lesioned with 6-OHDA and/or intoxicated with Mn-the most prominent impairments being in frontal cortex, striatum, and brain stem. In conclusion, ontogenetic Mn exposure, resulting in reactive oxygen species, HO(•) formation, represents a risk factor for dopaminergic neurotoxicity and development of neurodegenerative disorders.

Show MeSH
Related in: MedlinePlus