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

Abstract Hexavalent chromium (Cr (VI)) is a highly toxic metal. Exposure to Cr (VI) compounds may affect reproductive functions. Due to the importance of anterior pituitary hormones on reproductive physiology we have studied the effects of Cr (VI) on anterior pituitary. We previously demonstrated th...

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Bibliographic Details
Published in:Toxicology (Amsterdam) 2008-07, Vol.249 (2), p.109-115
Main Authors: Quinteros, Fernanda A, Machiavelli, Leticia I, Miler, Eliana A, Cabilla, Jimena P, Duvilanski, Beatriz H
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
Animals
Antioxidants - metabolism
Antioxidants - pharmacology
Apoptosis - drug effects
bcl-2-Associated X Protein - biosynthesis
bcl-2-Associated X Protein - genetics
Biological and medical sciences
Caspases - metabolism
Catalase - metabolism
Cells, Cultured
Chromium - toxicity
DNA Primers
Emergency
Hexavalent chromium
Male
Medical sciences
Oxidative stress
Oxidative Stress - drug effects
Pituitary
Pituitary Gland, Anterior - cytology
Pituitary Gland, Anterior - drug effects
Proto-Oncogene Proteins c-bcl-2 - metabolism
Rats
Rats, Wistar
Reactive Oxygen Species - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA - biosynthesis
RNA - isolation & purification
Tetrazolium Salts
Thiazoles
Toxicology
Tumor Suppressor Protein p53 - metabolism
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Summary:Abstract Hexavalent chromium (Cr (VI)) is a highly toxic metal. Exposure to Cr (VI) compounds may affect reproductive functions. Due to the importance of anterior pituitary hormones on reproductive physiology we have 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 the mechanisms involved in Cr (VI)-induced apoptosis we studied: (a) whether Cr (VI) affects the intracellular antioxidant response and (b) which of the apoptotic factors participates in Cr (VI) effect. Our results show that Cr (VI) treatment induces a decrease in catalase and glutathione peroxidase (GPx) activity but does not modify glutathione reductase (GR) activity. Cr (VI) exposure causes an increase of GSH levels. p53 and Bax mRNA are also upregulated by the metal. Pifithrin α, 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 apoptosis involves oxidative stress generation.
ISSN:0300-483X
1879-3185
DOI:10.1016/j.tox.2008.04.012