Tamoxifen inhibits mitochondrial membrane damage caused by disulfiram

Biochem Cell Biol. 2017 Oct;95(5):556-562. doi: 10.1139/bcb-2017-0027. Epub 2017 Jun 8.

Abstract

In this work, we studied the protective effects of tamoxifen (TAM) on disulfiram (Dis)-induced mitochondrial membrane insult. The results indicate that TAM circumvents the inner membrane leakiness manifested as Ca2+ release, mitochondrial swelling, and collapse of the transmembrane electric gradient. Furthermore, it was found that TAM prevents inactivation of the mitochondrial enzyme aconitase and detachment of cytochrome c from the inner membrane. Interestingly, TAM also inhibited Dis-promoted generation of hydrogen peroxide. Given that TAM is an antioxidant molecule, it is plausible that its protection may be due to the inhibition of Dis-induced oxidative stress.

Keywords: disulfiram; disulfirame; mitochondria; mitochondrie; oxidative stress; stress oxidant; tamoxifen; tamoxifène.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Disulfiram / adverse effects*
  • Mitochondrial Membranes / drug effects*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Membranes / pathology
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Tamoxifen / pharmacology*

Substances

  • Tamoxifen
  • Calcium
  • Disulfiram