Tamoxifen inhibits mitochondrial membrane damage caused by disulfiram

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