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The anticancer drug hydroxyurea (HU) at doses of 300-800 mg/kg/day causes a dramatic lethality (up to 100% after a 5-day treatment) in hypophysectomized as well as in adrenalectomized rats drinking physiological saline + 5% glucose. Mortality in controls was less than 10% over a 5-day period. Adrenal stimulatory or replacement therapies protect pituitary- or adrenal-ablated rats against HU toxicity. They also counteract white blood cell changes induced by the drug. HU (30-800 mg/kg) induces a dose-dependent increase of plasma corticosterone in normal rats after single or repeated treatments that is not observed in hypophysectomized animals. HU also increases plasma levels of epinephrine, although this finding cannot account for the rise in plasma corticosterone; indeed, it is secondary to a strong rise in plasma corticosterone. The stimulation of the hypothalamic-hypophyseal-adrenal axis induced by HU is responsible for the drug-induced adrenocortical activation. This activation appears to be a valuable defence mechanism protecting intact rats against HU lethality, and its failure causes the dramatic HU lethality in pituitary- or adrenal-ablated animals.
P Navarra, and
R Del Carmine, and
G Ciabattoni, and
M D'Amato, and
E Ragazzoni, and
M Vacca, and
A R Volpe, and
P Preziosi
January 1985,
Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement,
P Navarra, and
R Del Carmine, and
G Ciabattoni, and
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E Ragazzoni, and
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P Preziosi
June 1979,
Antimicrobial agents and chemotherapy,
P Navarra, and
R Del Carmine, and
G Ciabattoni, and
M D'Amato, and
E Ragazzoni, and
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January 1972,
Haematologica,
P Navarra, and
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M D'Amato, and
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M Vacca, and
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March 1993,
Endocrinology,
P Navarra, and
R Del Carmine, and
G Ciabattoni, and
M D'Amato, and
E Ragazzoni, and
M Vacca, and
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P Preziosi
October 2010,
Brain research,
P Navarra, and
R Del Carmine, and
G Ciabattoni, and
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July 1992,
Behavioral and neural biology,
P Navarra, and
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G Ciabattoni, and
M D'Amato, and
E Ragazzoni, and
M Vacca, and
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P Preziosi
October 1965,
The American journal of physiology,
P Navarra, and
R Del Carmine, and
G Ciabattoni, and
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P Preziosi
May 2014,
Japanese journal of clinical oncology,
P Navarra, and
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March 1994,
Chemico-biological interactions,
P Navarra, and
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G Ciabattoni, and
M D'Amato, and
E Ragazzoni, and
M Vacca, and
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April 1966,
Arztliche Forschung,
