TY - JOUR
T1 - Airborne manganese exposure differentially affects end points of oxidative stress in an age- and sex-dependent manner
AU - Erikson, Keith M.
AU - Dorman, David C.
AU - Lash, Lawrence H.
AU - Dobson, Allison W.
AU - Aschner, Michael
N1 - Funding Information:
This study was supported by funds from Ethyl Corporation, Richmond, VA. KE was supported by RJR-Leon Golberg fellowship in Pharmacology and Toxicology, and AD was supported by NIH T32-ES-07331, Multidisciplinary Training in Molecular Toxicology.
PY - 2004/7
Y1 - 2004/7
N2 - Juvenile female and male (young) and 16-mo-old male (old) rats inhaled manganese in the form of manganese sulfate (MnSO4) at 0, 0.01, 0.1, and 0.5 mg Mn/m3 or manganese phosphate at 0.1 mg Mn/m3 in exposures of 6 h/d, 5 d/wk for 13 wk. 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. Although most brain regions in the three groups of animals were unaffected by manganese exposure in terms of GS protein levels, there was significantly increased protein (p<0.05) in the hippocampus and decreased protein in the hypothalamus of young male rats exposed to manganese phosphate as well as in the aged rats exposed to 0.1 mg/m 3 MnSO4. Conversely, GS protein was elevated in the olfactory bulb of females exposed to the high dose of MnSO4. Statistically significant decreases (p<0.05) in MT and GS mRNA as a result of manganese exposure were observed in the cerebellum, olfactory bulb, and hippocampus in the young male rats, in the hypothalamus in the young female rats, and in the hippocampus in the senescent males. Total GSH levels significantly (p<0.05) decreased in the olfactory bulb of manganese exposed young male rats and increased in the olfactory bulb of female rats exposed to manganese. Both the aged and young female rats had significantly decreased (p<0.05) GSH in the striatum resulting from manganese inhalation. The old male rats also had depleted GSH levels in the cerebellum and hypothalamus as a result of the 0.1-mg/m3 manganese phosphate exposure. These results demonstrate that age and sex are variables that must be considered when assessing the neurotoxicity of manganese.
AB - Juvenile female and male (young) and 16-mo-old male (old) rats inhaled manganese in the form of manganese sulfate (MnSO4) at 0, 0.01, 0.1, and 0.5 mg Mn/m3 or manganese phosphate at 0.1 mg Mn/m3 in exposures of 6 h/d, 5 d/wk for 13 wk. 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. Although most brain regions in the three groups of animals were unaffected by manganese exposure in terms of GS protein levels, there was significantly increased protein (p<0.05) in the hippocampus and decreased protein in the hypothalamus of young male rats exposed to manganese phosphate as well as in the aged rats exposed to 0.1 mg/m 3 MnSO4. Conversely, GS protein was elevated in the olfactory bulb of females exposed to the high dose of MnSO4. Statistically significant decreases (p<0.05) in MT and GS mRNA as a result of manganese exposure were observed in the cerebellum, olfactory bulb, and hippocampus in the young male rats, in the hypothalamus in the young female rats, and in the hippocampus in the senescent males. Total GSH levels significantly (p<0.05) decreased in the olfactory bulb of manganese exposed young male rats and increased in the olfactory bulb of female rats exposed to manganese. Both the aged and young female rats had significantly decreased (p<0.05) GSH in the striatum resulting from manganese inhalation. The old male rats also had depleted GSH levels in the cerebellum and hypothalamus as a result of the 0.1-mg/m3 manganese phosphate exposure. These results demonstrate that age and sex are variables that must be considered when assessing the neurotoxicity of manganese.
KW - Brain
KW - Glutamine synthetase
KW - Glutathione
KW - Manganese
KW - Metallothionein
KW - Oxidative stress
KW - Rat
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U2 - 10.1385/bter:100:1:049
DO - 10.1385/bter:100:1:049
M3 - Article
C2 - 15258319
AN - SCOPUS:4043074117
SN - 0163-4984
VL - 100
SP - 49
EP - 62
JO - Biological Trace Element Research
JF - Biological Trace Element Research
IS - 1
ER -