title: Protective behavior of tamoxifen against Hg2+-induced toxicity on kidney mitochondria: in vitro and in vivo experiments.
abstract: Heavy metals are known to induce functional alterations in kidney mitochondria, this damage plays a central role in the mercury-induced acute renal failure. In fact, mercury causes rapid and dramatic changes in the membrane's ionic permeability in such a way that a supra load of mitochondrial Ca(2+) occurs. As a consequence, the phenomenon of permeability transition takes place. In this work we studied in vitro and in vivo the protective effect of the selective estrogen receptor modulator tamoxifen on the deleterious action of mercury-induced nonselective permeability in kidney mitochondria. Added in vitro tamoxifen inhibited membrane nonspecific pore opening, brought about by Hg(2+), as well as the oxidative damage of the enzyme cis-aconitase. In vivo the administration of tamoxifen prevented Hg(2+)-induced poisoning on mitochondrial energy-dependent functions. Permeability transition was analyzed by measuring matrix Ca(2+) retention, mitochondrial swelling, and the build up and maintenance of a transmembrane electric gradient. The pharmacologic action of tamoxifen on mercury poisoning could be ascribed to its cyclosporin-like action.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Tlalpan, DF 014080, Mexico.
authors.forename: Luz
authors.initials: L
authors.lastname: Hernández-Esquivel
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zazueta
authors.forename: Mabel
authors.initials: M
authors.lastname: Buelna-Chontal
authors.forename: Sauri
authors.initials: S
authors.lastname: Hernández-Reséndiz
authors.forename: Natalia
authors.initials: N
authors.lastname: Pavón
authors.forename: Edmundo
authors.initials: E
authors.lastname: Chávez
mesh_terms: D000818:Animals; D007668:Kidney / Q000187:drug effects*; D008628:Mercury / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D013629:Tamoxifen; D008628:Mercury