Tamoxifen inhibits mitochondrial oxidative stress damage induced by copper orthophenanthroline

Abstract

In this work, we studied the effect of tamoxifen and cyclosporin A on mitochondrial permeability transition caused by addition of the thiol-oxidizing pair Cu -orthophenanthroline. The findings indicate that tamoxifen and cyclosporin A circumvent the oxidative membrane damage manifested by matrix Ca release, mitochondrial swelling, and transmembrane electrical gradient collapse. Furthermore, it was found that tamoxifen and cyclosporin A prevent the generation of TBARs promoted by Cu -orthophenanthroline, as well as the inactivation of the mitochondrial enzyme aconitase and disruption of mDNA. Electrophoretic analysis was unable to demonstrate a cross-linking reaction between membrane proteins. Yet, it was found that Cu -orthophenanthroline induced the generation of reactive oxygen species. It is thus plausible that membrane leakiness is due to an oxidative stress injury.

Tamoxifen inhibits mitochondrial membrane damage caused by disulfiram

“…Inhibition of permeability transition can be attained by different sort of reagents; indeed, immunosuppressant cyclosporine A is the most effective. Tamoxifen has recently been identified as an effective inhibitor of membrane leakage (Custodio et al, 1998;Buelna-Chontal et al, 2016).…”

“…Specifically, this compound is a selective estrogen receptor modulator widely used in the oncology and reproductive endocrinology (Birznice et al, 2010). Tamoxifen has also been demonstrated to possess antioxidant properties (Custodio et al, 1998;Buelna-Chontal et al, 2016). It is important to note that the protection obtained with tamoxifen on the pore-opening action of disulfiram presents relevant information on the mechanism involved.…”