title: 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 Cu2+-orthophenanthroline. The findings indicate that tamoxifen and cyclosporin A circumvent the oxidative membrane damage manifested by matrix Ca2+release, mitochondrial swelling, and transmembrane electrical gradient collapse. Furthermore, it was found that tamoxifen and cyclosporin A prevent the generation of TBARs promoted by Cu2+-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 Cu2+-orthophenanthroline induced the generation of reactive oxygen species. It is thus plausible that membrane leakiness is due to an oxidative stress injury.
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Ignacio Chávez, D.F. México, México.
authors.forename: Mabel
authors.initials: M
authors.lastname: Buelna-Chontal
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, D.F. México, 14080, México.
authors.forename: Luz
authors.initials: L
authors.lastname: Hernández-Esquivel
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Ignacio Chávez, D.F. México, México.
authors.forename: Francisco
authors.initials: F
authors.lastname: Correa
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Ignacio Chávez, D.F. México, México.
authors.forename: Jorge Luis
authors.initials: JL
authors.lastname: Díaz-Ruiz
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, D.F. México, 14080, México.
authors.forename: Edmundo
authors.initials: E
authors.lastname: Chávez
mesh_terms: D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D003300:Copper / Q000633:toxicity*; D016572:Cyclosporine / Q000494:pharmacology; D004272:DNA, Mitochondrial / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009942:Organometallic Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010618:Phenanthrolines / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D009942:Organometallic Compounds; D010618:Phenanthrolines; D020011:Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; C464760:copper-1,10-phenanthroline; D013629:Tamoxifen; D003300:Copper; D016572:Cyclosporine; D006861:Hydrogen Peroxide; D005978:Glutathione; D002118:Calcium
keywords: copper; mitochondria; oxidative stress; permeability transition; tamoxifen