Protective behavior of tamoxifen against Hg²⁺-induced toxicity on kidney mitochondria: In vitro and in vivo experiments

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• 作者：Luz  ; Hern&aacute ; ndez-Esquivel ; Cecilia  ; Zazueta ; Mabel  ; Buelna-Chontal ; Sauri  ; Hern&aacute ; ndez-Resé ; ndiz ; Natalia  ; Pavó ; n ; Edmundo  ; Ch&aacute ; vez  ; ;   ; ^{echavez@salud.gob.mx}
• 关键词：Tamoxifen ; Mercury toxicity ; Mitochondria ; Permeability transition ; Calcium
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2011
• 出版时间：November 2011
• 年：2011
• 卷：127
• 期：3-5
• 页码：345-350
• 全文大小：285 K

文摘

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 Ca²⁺ 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 Hg²⁺, as well as the oxidative damage of the enzyme cis-aconitase. In vivo the administration of tamoxifen prevented Hg²⁺-induced poisoning on mitochondrial energy-dependent functions. Permeability transition was analyzed by measuring matrix Ca²⁺ 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.