Tamoxifen and its metabolites induce mitochondrial membrane depolarization and caspase-3 activation in equine neutrophils

Vet Med Sci. 2020 Nov;6(4):673-678. doi: 10.1002/vms3.316. Epub 2020 Jun 17.

Abstract

Neutrophils participate in innate immunity as the first line of host defence against microorganisms. However, persistent neutrophil activity and delayed apoptosis can be harmful to surrounding tissues; this problem occurs in diverse inflammatory diseases, including asthma-affected horses. Previous studies in horses with acute lung inflammation indicated that treatment with tamoxifen (TX), a selective oestrogen receptor modulator, produces a significant decrease in bronchoalveolar lavage fluid (BALF) neutrophil content. The aim of this study was to investigate the effect of tamoxifen and its metabolites (N-desmethyltamoxifen and endoxifen) on the mitochondrial membrane potential assay by flow cytometry, and the activation of effector caspase-3 through immunoblotting, in peripheral blood neutrophils obtained from healthy horses (n = 5). Results show that tamoxifen, N-desmethyltamoxifen and endoxifen depolarize the mitochondrial membrane and activate caspase-3 in healthy equine neutrophils in vitro. These findings suggest that tamoxifen and its metabolites may activate the intrinsic apoptotic pathway in equine neutrophils. However, more studies are necessary to further explore the signalling pathways of these drugs in the induction of apoptosis.

Keywords: Tamoxifen; apoptosis; horses; neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / pharmacology*
  • Caspase 3 / immunology*
  • Female
  • Flow Cytometry / veterinary
  • Horses / immunology*
  • Immunity, Innate / drug effects*
  • Immunoblotting / veterinary
  • Male
  • Mitochondrial Membranes / drug effects*
  • Mitochondrial Membranes / physiology
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacology*

Substances

  • Anti-Asthmatic Agents
  • Tamoxifen
  • 4-hydroxy-N-desmethyltamoxifen
  • Caspase 3
  • N-desmethyltamoxifen