Mechanisms of chromium (VI)-induced apoptosis in anterior pituitary cells

AF QUINTEROS; LI MACHIAVELLI; E. MILER; JP CABILLA; BH DUVILANSKI

TOXICOLOGY

Elsevier

Año: 2008 vol. 249 p. 109 - 115

0300-483X

Hexavalent chromium (Cr (VI)) is a highly toxic metal. Exposure to Cr (VI) compounds may affect reproductivefunctions. Due to the importance of anterior pituitary hormones on reproductive physiology wehave studied the effects of Cr (VI) on anterior pituitary.We previously demonstrated that, after in vivo Cr(VI) administration, Cr accumulates in the pituitary gland and affects prolactin secretion. In vitro, Cr (VI)causes apoptosis in anterior pituitary cells due to oxidative stress generation. To better understand themechanisms involved in Cr (VI)-induced apoptosiswe studied: (a) whether Cr (VI) affects the intracellularantioxidant response and (b) which of the apoptotic factors participates in Cr (VI) effect. Our results showthat Cr (VI) treatment induces a decrease in catalase and glutathione peroxidase (GPx) activity but doesnot modify glutathione reductase (GR) activity. Cr (VI) exposure causes an increase of GSH levels. p53and Bax mRNA are also upregulated by the metal. Pifithrin , a p53 transcriptional inhibitor, increases Cr(VI) cytotoxicity, suggesting a role of p53 as a survival molecule. The antioxidant N-acetyl-cysteine (NAC)could prevent Bax mRNA increase and caspase 3 activation, confirming that Cr (VI)-induced apoptosisinvolves oxidative stress generation.