title: Effects of manganese (Mn) on the developing rat brain: oxidative-stress related endpoints.
abstract: We evaluated biochemical endpoints related to oxidative stress in brains of neonatal rats exposed to manganese (Mn). Oral Mn chloride (MnCl2) (0, 25, or 50 mg Mn chloride kg(-1) body weight per day) was given daily to neonatal rats throughout lactation (i.e. from postnatal day (PND) 1 to 21). As previously reported by [J. Appl. Toxicol. 20 (2000) 179], this treatment paradigm results in increased cerebral cortex (CTX) Mn concentrations in PND 21 rats from both Mn treatment groups. High dose Mn exposure also results in increased cerebellar Mn concentrations. This preliminary study determined whether this exposure paradigm also affects cerebrocortical or cerebellar metallothionein (MT) mRNA levels, glutamine synthetase (GS) activity, GS protein levels, as well as total glutathione (GSH) levels. High dose Mn exposure significantly increased (P < 0.05) total cerebrocortical GSH without accompanying changes in any of the other measured parameters. Therefore, it is unlikely that high dose Mn exposure is associated with oxidative stress in this experimental paradigm.
authors.affiliation: Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1083, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weber
authors.forename: David C
authors.initials: DC
authors.lastname: Dorman
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Lash
authors.forename: Keith
authors.initials: K
authors.lastname: Erikson
authors.forename: Kent E
authors.initials: KE
authors.lastname: Vrana
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis; D005978:Glutathione / Q000096:biosynthesis; D017895:Manganese Compounds / Q000494:pharmacology*; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; D012333:RNA, Messenger; D008668:Metallothionein; D005974:Glutamate-Ammonia Ligase; D005978:Glutathione; C025340:manganese chloride