Arsenic species, AS3MT amount, and AS3MT gene expression in different brain regions of mouse exposed to arsenite.
Human exposure to inorganic arsenic (iAs) has been associated with cancer and serious injury to various internal organs, as well as peripheral neuropathy, endocrine disruption and diverse effects in the central nervous system (CNS). Using rodent models, it is possible to demonstrate As accumulation in the brain that leads to defects in operant learning, behavioral changes, and affect pituitary gonadotrophins. iAs biomethylation in the CNS is a significant process, yielding products that are more reactive and toxic than the parent compound. Mice received 2.5, 5, and 10 mg/kg/day sodium arsenite orally for 9 days. We investigated the distribution of iAs and its metabolites as well as the mRNA and protein expression of arsenic (III) methyltransferase (AS3MT), which encodes the key enzyme in iAs metabolism, in the cerebral cortex, hippocampus, striatum, mesencephalon, thalamus, cerebellum, hypothalamus, pons, medulla oblongata, and pituitary of mouse brain. Our findings show that methylated As metabolites are present in all brain regions studied suggesting that AS3MT is ubiquitously expressed in the brain and it is not inducible by dose of arsenite. There is also a dose-related accumulation of As species in all brain regions, with the highest accumulation observed in the pituitary. The higher distribution of arsenicals in pituitary can help to explain the neuroendocrine effects associated with iAs exposure.
Departamento de Toxicología, CINVESTAV, México.
Luz C
LC
Sánchez-Peña
Pavel
P
Petrosyan
Mariana
M
Morales
Nydia B
NB
González
Gabriel
G
Gutiérrez-Ospina
Luz M
LM
Del Razo
Maria E
ME
Gonsebatt
D000818:Animals; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D018053:Arsenites / Q000493:pharmacokinetics / Q000633:toxicity; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017670:Sodium Compounds / Q000493:pharmacokinetics / Q000633:toxicity
D018053:Arsenites; D017670:Sodium Compounds; C017947:sodium arsenite; D008780:Methyltransferases; C532135:AS3MT protein, mouse; D001151:Arsenic