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Titolo:
Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure
Autore:
Silva, MMC; Madeira, VMC; Almeida, LM; Custodio, JBA;
Indirizzi:
Univ Coimbra, Fac Farm, Lab Bioquim, P-3000 Coimbra, Portugal Univ Coimbra Coimbra Portugal P-3000 b Bioquim, P-3000 Coimbra, Portugal Univ Coimbra, Ctr Neurociencias, P-3049 Coimbra, Portugal Univ Coimbra Coimbra Portugal P-3049 ociencias, P-3049 Coimbra, Portugal
Titolo Testata:
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
fascicolo: 1, volume: 1464, anno: 2000,
pagine: 49 - 61
SICI:
0005-2736(20000315)1464:1<49:HOHEIB>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTICANCER DRUG TAMOXIFEN; RADICAL CHAIN OXIDATION; BREAST-CANCER-CELLS; ESTROGEN-RECEPTOR; ALPHA-TOCOPHEROL; INHIBITS GROWTH; HUMAN-TISSUES; BINDING-SITE; VITAMIN-E; IN-VITRO;
Keywords:
tamoxifen; human erythrocyte; hemolysis; oxidative stress; partition coefficient; membrane disruption;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Custodio, JBA Univ Coimbra, Fac Farm, Lab Bioquim, Couraca Apostolos 51,R-C, P-3000 Coimbra, Portugal Univ Coimbra Couraca Apostolos 51,R-C Coimbra Portugal P-3000
Citazione:
M.M.C. Silva et al., "Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure", BBA-BIOMEMB, 1464(1), 2000, pp. 49-61

Abstract

Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanismson TAM-induced hemolytic anemia and the involvement of biomembranes in itscytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 mu M TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore,it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K+ from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocytemembrane is consequently avoided. Therefore, TAM-induced hemolysis resultsfrom a structural perturbation of red cell membrane, leading to changes inthe framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 04:53:29