Oral zeranol shortens the prolonged bleeding time of uremic rats

Carla Zoja, Gianluigi Viganò, Daniela Corna, Mario Salmona, Giuseppe Remuzzi, Silvio Garattini

Research output: Contribution to journalArticlepeer-review

Abstract

Intravenous conjugated estrogens reduce the prolonged bleeding time in uremic patients and in a rat model of uremia. However, estrogens have major side effects related to their hormonal activity. We investigated whether a β-resorcylic acid lactone, zeranol (a compound with close spatial similarity to estrogens but with a weak estrogenic activity), improves primary hemostasis in uremic rats and whether the effect is mediated by estrogen receptors. The results showed that single oral administration of zeranol significantly (P <0.01) shortened the bleeding time of uremic rats, 20 mg/kg being the minimum effective dose. This effect was long-lasting (72 hours). The dose of 30 mg/kg zeranol reproduced the pattern observed after 20 mg/kg but bleeding time values were still significantly (P <0.01) shortened 96 hours after the administration. No changes in hematocrit, platelet and leukocyte count, and serum creatinine were detected after zeranol administration. When uremic rats were pre-treated orally with two estrogen receptor antagonists tamoxifen and clomiphene (3 mg/kg), zeranol did not shorten the bleeding time, thus suggesting that the hemostatic effect of zeranol was due to an estrogen receptor-mediated mechanism. These results might have important future implications for the management of uremic bleeding in humans.

Original languageEnglish
Pages (from-to)96-100
Number of pages5
JournalKidney International
Volume38
Issue number1
Publication statusPublished - Jul 1990

ASJC Scopus subject areas

  • Nephrology

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