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

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

Research output: Contribution to journalArticle

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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Tamoxifen
Nitric Oxide
Blood Platelets
Platelet Aggregation
Superoxides
Thrombosis
Platelet Aggregation Inhibitors
Estradiol
Breast Neoplasms

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

The effect of tamoxifen and its metabolites on platelet function and nitric oxide release. / Deak, Leslie R.; Burack, Vicki; Flockhart, Dave; Freedman, Jane E.

In: Clinical Pharmacology and Therapeutics, Vol. 69, No. 2, 01.12.2001, p. P32.

Research output: Contribution to journalArticle

Deak, LR, Burack, V, Flockhart, D & Freedman, JE 2001, 'The effect of tamoxifen and its metabolites on platelet function and nitric oxide release', Clinical Pharmacology and Therapeutics, vol. 69, no. 2, pp. P32.
Deak, Leslie R. ; Burack, Vicki ; Flockhart, Dave ; Freedman, Jane E. / The effect of tamoxifen and its metabolites on platelet function and nitric oxide release. In: Clinical Pharmacology and Therapeutics. 2001 ; Vol. 69, No. 2. pp. P32.
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