Endocrine Abstracts

Exposure to arsenic (As) through consumption of contaminated water is considered one of the top environmental health threats worldwide. Human exposure to As has been associated with cancer of several organs, neurological disorders and reproductive problems. Nevertheless, there are no reports on the effect of As on anterior pituitary gland and little is known about the effect of As on hormone release. We have previously shown that 25 μM As (as sodium arsenite) reduces prolactin release and pituitary cell viability after 24 h. The aim of the present work was to study the mechanisms of arsenic citotoxicity in primary anterior pituitary cultures from male Wistar rats. Arsenic decreased cell viability from 9 h of treatment (MTT assay, Abs. 600 nm, % of control (C); 9 h: 83.6 2.8*, 18h: 82.2 5.4*, 24h: 70.3 2.6***; *P<0.05; ***P<0.001 vs. C). Apoptotic morphology became evident after 18 and 24 h of As exposure (% apoptotic nuclei/total nuclei; C: 3.3 0.5, 9h: 4.9 1.2; 18h: 10.3 1.4**; 24h: 11.8 1.3**; **P<0.01 vs. C). Mitochondrial membrane potential (DiOC6 by flow citometry) was significantly reduced after 6 h of As exposure. In parallel, there was an early increase in reactive oxygen species levels during the first hour of As exposure (DHR 123 by flow citometry). Arsenic modified mRNA expression of stress response genes [relative units as % of C, heme oxygenase-1 (3h: 172; 6h: 128; 9h: 174); metallothionein-1 (3h: 174; 6h: 121; 9h: 160); nitric oxide synthase-1 (3h: 82; 6h: 71; 9h: 96)]. Antioxidant treatment with N-acetyl-cysteine (NAC) was able to partially reverse As-induced apoptosis (annexin V- propidium iodide staining, % of C, As: 243.6; As+NAC: 180.5). These results suggest that As citotoxic action on anterior pituitary cells is produced by an apoptotic process which can begin with an imbalance on cell redox status.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.