title: Persistent alterations in biomarkers of oxidative stress resulting from combined in utero and neonatal manganese inhalation.
abstract: Neonatal female and male rats were exposed to airborne manganese sulfate (MnSO4) during gestation and postnatal d 1-18. Three weeks postexposure, 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.
authors.affiliation: Department of Nutrition, University of North Carolina Greensboro, Greensboro, NC 27402-6170, USA.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Erikson
authors.forename: David C
authors.initials: DC
authors.lastname: Dorman
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Lash
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage; D020149:Manganese Poisoning / Q000378:metabolism*; D008668:Metallothionein / Q000097:blood; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013431:Sulfates / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D017895:Manganese Compounds; D012333:RNA, Messenger; D013431:Sulfates; D008668:Metallothionein; D005974:Glutamate-Ammonia Ligase; D005978:Glutathione; C039798:manganese sulfate