Effects of manganese (Mn) on the developing rat brain: oxidative-stress related endpoints.
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.
Weber
Sarah
S
Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1083, USA.
Dorman
David C
DC
Lash
Lawrence H
LH
Erikson
Keith
K
Vrana
Kent E
KE
Aschner
Michael
M
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
D002712:Chlorides; D017895:Manganese Compounds; D012333:RNA, Messenger; D008668:Metallothionein; D005974:Glutamate-Ammonia Ligase; D005978:Glutathione; C025340:manganese chloride