TY - JOUR
T1 - Persistent alterations in biomarkers of oxidative stress resulting from combined in utero and neonatal manganese inhalation
AU - Erikson, Keith M.
AU - Dorman, David C.
AU - Lash, Lawrence H.
AU - Aschner, Michael
N1 - Funding Information:
This study was supported by funds from Ethyl Corporation, Richmond, VA.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/5
Y1 - 2005/5
N2 - Neonatal female and male rats were exposed to airborne manganese sulfate (MnSO4) during gestation and postnatal d 1-18. Three weeks post-exposure, rats were killed and we assessed biochemical end points indicative of oxidative stress in five brain regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum. Glutamine synthetase (GS) protein levels, metallothionein (MT) and GS mRNA levels, and total glutathione (GSH) levels were determined for all five regions. Overall, there was a statistically significant effect of manganese exposure on decreasing brain GS protein levels (p=0.0061), although only the highest dose of manganese (1 mg Mn/m3) caused a significant increase in GS messenger RNA (mRNA) in both the hypothalamus and olfactory bulb of male rats and a significant decrease in GS mRNA in the striatum of female rats. This highest dose of manganese had no effect on MT mRNA in either males or females; however, the lowest dose (0.05 mg Mn/m3) decreased MT mRNA in the hippocampus, hypothalamus, and striatum in males. The median dose (0.5 mg Mn/m3) led to decreased MT mRNA in the hippocampus and hypothalamus of the males and olfactory bulb of the females. Overall, manganese exposure did not affect total GSH levels, a finding that is contrary to those in our previous studies. Only the cerebellum of manganese-exposed young male rats showed a significant reduction (p<0.05) in total GSH levels compared to control levels. These data reveal that alterations in biomarkers of oxidative stress resulting from in utero and neonatal exposures of airborne manganese remain despite 3 wk of recovery; however, it is important to note that the doses of manganese utilized represent levels that are 100-fold to a 1000-fold higher than the inhalation reference concentration set by the US Environmental Protection Agency.
AB - Neonatal female and male rats were exposed to airborne manganese sulfate (MnSO4) during gestation and postnatal d 1-18. Three weeks post-exposure, rats were killed and we assessed biochemical end points indicative of oxidative stress in five brain regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum. Glutamine synthetase (GS) protein levels, metallothionein (MT) and GS mRNA levels, and total glutathione (GSH) levels were determined for all five regions. Overall, there was a statistically significant effect of manganese exposure on decreasing brain GS protein levels (p=0.0061), although only the highest dose of manganese (1 mg Mn/m3) caused a significant increase in GS messenger RNA (mRNA) in both the hypothalamus and olfactory bulb of male rats and a significant decrease in GS mRNA in the striatum of female rats. This highest dose of manganese had no effect on MT mRNA in either males or females; however, the lowest dose (0.05 mg Mn/m3) decreased MT mRNA in the hippocampus, hypothalamus, and striatum in males. The median dose (0.5 mg Mn/m3) led to decreased MT mRNA in the hippocampus and hypothalamus of the males and olfactory bulb of the females. Overall, manganese exposure did not affect total GSH levels, a finding that is contrary to those in our previous studies. Only the cerebellum of manganese-exposed young male rats showed a significant reduction (p<0.05) in total GSH levels compared to control levels. These data reveal that alterations in biomarkers of oxidative stress resulting from in utero and neonatal exposures of airborne manganese remain despite 3 wk of recovery; however, it is important to note that the doses of manganese utilized represent levels that are 100-fold to a 1000-fold higher than the inhalation reference concentration set by the US Environmental Protection Agency.
KW - Brain
KW - Glutamine synthetase
KW - Glutathione
KW - In utero
KW - Manganese
KW - Metallothionein
KW - Rat
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U2 - 10.1385/BTER:104:2:151
DO - 10.1385/BTER:104:2:151
M3 - Article
C2 - 15894815
AN - SCOPUS:23844485986
SN - 0163-4984
VL - 104
SP - 151
EP - 163
JO - Biological Trace Element Research
JF - Biological Trace Element Research
IS - 2
ER -