The effect of tamoxifen and its metabolites on platelet function and nitric oxide release

Leslie R. Deak, Vicki Burack, Dave Flockhart, Jane E. Freedman

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Abstract

Tamoxifen is used for the prevention and treatment of breast cancer and its use is associated with an increased risk of thrombosis. Thrombus formation can be decreased by nitric oxide (NO), an inhibitor of platelet function. Therefore, the effect of tamoxifen on platelet activity and platelet NO release was determined. Platelets were incubated with tamoxifen (0.1 mM) or the tamoxifen metabolites 4-hydroxy-tomoxifen (4-OH) or N-desmethyl tamoxifen (NDM) followed by incubation with 17βestradiol (0.01 μM) or vehicle control. Incubation with estradiol alone led to modest inhibition of platelet aggregation, and an increase in NO release (P<0.05). Only NDM significantly increased platelet aggregation (P=0.05). Platelet NO release significantly decreased after incubation with tamoxifen, NDM, or 4-OH (P<0.05). Platelet superoxide release increased with tamoxifen, NDM, or 4-OH (P<0.05). In summary, all tested forms of tamoxifen decreased platelet release of NO and enhanced superoxide production. These data suggest that release of platelet NO is involved in the pro-thrombotic action of tamoxifen.

Original languageEnglish (US)
Pages (from-to)P32
JournalClinical Pharmacology and Therapeutics
Volume69
Issue number2
StatePublished - Dec 1 2001

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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