Adrenocortical activation is independent from systemic toxicity in long-term hydroxyurea treatment

Abstract

Plasma corticosterone, haematology, and blood chemistry parameters were unaffected by treatment of male rats with hydroxyurea (HYD) at a dosage of 80 mg/kg/day for a 2-week period; this dosage is used in cancer chemotherapy schedules. Conversely, treatment of male rats with HYD at 300 mg/kg/day or 800 mg/kg every third day, for a period of 2 weeks increased the levels of plasma corticosterone by 80% and 268% respectively 2 hours after the 14th administration; these dosages are up to 10 times higher than those employed in cancer chemotherapy. The higher corticosterone levels were found following a treatment schedule which resulted in a reduced effect on haematology and blood chemistry parameters than those found with daily dosages of 300 mg/kg. The data suggest that hypophyseal-adrenocortical activation by HYD is unrelated to systemic drug toxicity and that it is a unique feature of this anti-cancer drug. Adrenalectomy in rats greatly increased the effects of HYD administered at dosages of 300 on the haematological parameters and survival