Apoptosis induced by arsenic is partially reverted by antioxidants in anterior pituitary cells.

RONCHETTI S; NUDLER S; CABILLA J; GONSEBATT M

Florencia

Congreso; 15th International Congress of Endocrinology; 2012

International Society of Endocrinology

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 micromolar 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. Apoptotic morphology became evident after 18 and 24 h of As exposure. Mitochondrial membrane potential 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. Arsenic modified mRNA expression of stress response genes heme oxygenase-1; metallothionein-1; nitric oxide synthase-1. Antioxidant treatment with N-acetyl-cysteine (NAC) was able to partially reverse As-induced apoptosis. 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.