title: In Vivo and In Vitro Arsenic Exposition Induces Oxidative Stress in Anterior Pituitary Gland.
abstract: Inorganic arsenic (iAs) is at the top of toxic metalloids. Inorganic arsenic-contaminated water consumption is one of the greatest environmental health threats worldwide. Human iAs exposure has been associated with cancers of several organs, neurological disorders, and reproductive problems. Nevertheless, there are no reports describing how iAs affects the anterior pituitary gland. The aim of this study was to investigate the mechanisms involved in iAs-mediated anterior pituitary toxicity both in vivo and in vitro. We showed that iAs administration (from 5 to 100 ppm) to male rats through drinking water increased messenger RNA expression of several oxidative stress-responsive genes in the anterior pituitary gland. Serum prolactin levels diminished, whereas luteinizing hormone (LH) levels were only affected at the higher dose tested. In anterior pituitary cells in culture, 25 µmol/L iAs significantly decreased prolactin release in a time-dependent fashion, whereas LH levels remained unaltered. Cell viability was significantly reduced mainly by apoptosis evidenced by morphological and phosphatidylserine externalization studies. This process is characterized by early depolarization of mitochondrial membrane potential and increased levels of reactive oxygen species. Expression of some key oxidative stress-responsive genes, such as heme oxygenase-1 and metallothionein-1, was also stimulated by iAs exposure. The antioxidant N-acetyl cysteine prevented iAs-induced effects on the expression of oxidative stress markers, prolactin release, and apoptosis. In summary, the present work demonstrates for the first time that iAs reduces prolactin release both in vivo and in vitro and induces apoptosis in anterior pituitary cells, possibly resulting from imbalanced cellular redox status.
authors.affiliation: Facultad de Medicina, Instituto de Investigaciones Biomédicas (UBA-CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina sronchettibiol@gmail.com jcabilla@ffyb.uba.ar.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Ronchetti
authors.affiliation: Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires, Argentina.
authors.forename: María S
authors.initials: MS
authors.lastname: Bianchi
authors.affiliation: Facultad de Medicina, Instituto de Investigaciones Biomédicas (UBA-CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Beatriz H
authors.initials: BH
authors.lastname: Duvilanski
authors.affiliation: Facultad de Medicina, Instituto de Investigaciones Biomédicas (UBA-CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Jimena P
authors.initials: JP
authors.lastname: Cabilla
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001151:Arsenic / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008668:Metallothionein / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: C491055:Mt2A protein, rat; D017382:Reactive Oxygen Species; C495697:Txn1 protein, rat; D014874:Water Pollutants, Chemical; D013879:Thioredoxins; D011388:Prolactin; D008668:Metallothionein; D001151:Arsenic
keywords: anterior pituitary cells; apoptosis; arsenic; oxidative stress