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Titolo:
Hydroxytamoxifen interaction with human erythrocyte membrane and inductionof permeabilization and subsequent hemolysis
Autore:
Silva, MMC; Madeira, VMC; Almeida, LM; Custodio, JBA;
Indirizzi:
Fac Farm, Lab Bioquim, P-3000 Coimbra, Portugal Fac Farm Coimbra Portugal P-3000 , Lab Bioquim, P-3000 Coimbra, Portugal Univ Coimbra, Ctr Neurociencias Coimbra, P-3000 Coimbra, Portugal Univ Coimbra Coimbra Portugal P-3000 s Coimbra, P-3000 Coimbra, Portugal
Titolo Testata:
TOXICOLOGY IN VITRO
fascicolo: 6, volume: 15, anno: 2001,
pagine: 615 - 622
SICI:
0887-2333(200112)15:6<615:HIWHEM>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
RADICAL CHAIN OXIDATION; BREAST-CANCER; ALPHA-TOCOPHEROL; VITAMIN-E; ESTROGEN-RECEPTOR; TAMOXIFEN; METABOLITES; IDENTIFICATION; INHIBITION; BINDING;
Keywords:
4-hydroxytamoxifen; tamoxifen; human erythrocytes; hemolysis; oxidative stress; osmotic swelling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Custodio, JBA Fac Farm, Lab Bioquim, P-3000 Coimbra, Portugal Fac Farm Coimbra Portugal P-3000 P-3000 Coimbra, Portugal
Citazione:
M.M.C. Silva et al., "Hydroxytamoxifen interaction with human erythrocyte membrane and inductionof permeabilization and subsequent hemolysis", TOX VITRO, 15(6), 2001, pp. 615-622

Abstract

4-hydroxytamoxifen (OHTAM) is the most active metabolite of the widely prescribed anticancer drug tamoxifen (TAM) used in breast cancer therapy. Thiswork describes the effects of OHTAM on isolated human erythrocytes, using standardized test conditions, to check for a putative contribution to the TAM-induced hemolysis and to study basic mechanisms involved in the interaction of OHTAM with cell membranes. Incubation of isolated human erythrocyteswith relatively high concentrations of OHTAM results in a concentration-dependent hemolysis, its hemolytic effect being about one-third of that induced by TAM. OHTAM-induced hemolysis is prevented by either alpha -tocopherol(alpha -T) or alpha -tocopherol acetate (alpha -TAc) and it occurs in the absence of oxygen consumption and hemoglobin oxidation, ruling out the oxidative damage of erythrocytes. However, OHTAM remarkably increases the osmotic fragility of erythrocytes, increasing the susceptibility of erythrocytesto hypotonic lysis. Additionally, the hemoglobin release induced by OHTAM is preceded by a rapid efflux of intracellular K+. Therefore, our data suggest that OHTAM-induced hemolysis does not contribute to TAM-induced hemolytic anemia and it is a much weaker toxic drug as compared with TAM. Moreover, at variance with the membrane disrupting effects of TAM, OHTAM promotes perturbation of the membrane's backbone region due to its strong binding to proteins with consequent formation of membrane paths of permeability to small solutes and retention of large solutes like hemoglobin, followed by osmotic swelling and cell lysis. The prevention of OHTAM-induced hemolysis by alpha -T and alpha -TAc is probably committed to the permeability sealing resulting from structural stabilization of membrane. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 19:23:46