Cadmium induces apoptosis in anterior pituitary cells that can be reversed by treatment with antioxidants.
Cadmium (Cd(2+)) is an ubiquitous toxic metal that is involved in a variety of pathological conditions. Several reports indicate that Cd(2+) alters normal pituitary hormone secretion; however, little is known about the mechanisms that induce this misregulation. This paper reports the effect of Cd(2+) on anterior pituitary cell viability and its relation to prolactin secretion. Cd(2+) concentrations above 10 microM were found to be cytotoxic for pituitary cells. Morphological studies as well as DNA ladder fragmentation and caspase activation showed that Cd(2+)-treated cells undergo apoptosis. Even though several hours were needed to detect Cd(2+)-induced cytotoxicity, the effect of the metal became irreversible very quickly, requiring only 3 h of treatment. Prolactin release (measured at 48 h) was inhibited when the cells were exposed to Cd(2+) for 1 h, before any change in cell viability was observed. The antioxidants N-acetyl-cysteine and Trolox (a hydrosoluble derivative of vitamin E), but not ascorbic acid, reversed both Cd(2+)-mediated cytotoxicity and the inhibition of prolactin release, supporting the involvement of oxidative stress in the mechanism of Cd(2+) action. In summary, the present work demonstrates that Cd(2+) is cytotoxic for anterior pituitary cells, that this effect is due to an induction of apoptosis, and that it can be reversed by antioxidants.
Poliandri
Ariel H B
AH
Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires C1121ABG, Argentina.
Cabilla
Jimena P
JP
Velardez
Miguel O
MO
Bodo
Cristian C A
CC
Duvilanski
Beatriz H
BH
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006728:Hormones / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013778:Tetrazolium Salts; D013844:Thiazoles; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D006728:Hormones; D013778:Tetrazolium Salts; D013844:Thiazoles; D002104:Cadmium; D014810:Vitamin E; D011388:Prolactin; D020169:Caspases; C022616:thiazolyl blue; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000111:Acetylcysteine