Fermented papaya preparation as redox regulator in blood cells of β-thalassemic mice and patients

被引:37
作者
Amer, Johnny [1 ]
Goldfarb, Ada [1 ]
Rachmilewitz, Eliezer A. [2 ]
Fibach, Eitan [1 ]
机构
[1] Hadassah Hebrew Univ, Med Ctr, Dept Hematol, Jerusalem, Israel
[2] E Wolfson Med Ctr, Dept Hematol, Holon, Israel
关键词
hemoglobinopathies; free radicals; antioxidants; flow cytometry;
D O I
10.1002/ptr.2379
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Many aspects of the pathology in beta-hemoglobinopathies (beta-thalassemia and sickle cell anemia) are mediated by oxidative stress. Fermented papaya preparation (FPP) was tested for its antioxidant effects: the scavenging effect was determined spectrofluorometrically in a cell-free system using 2'-7'-dichlorofluorescin-diacetate (DCF). Both spontaneous and H2O2-induced DCF oxidations were decreased by FPP in a dose-dependent fashion. Using flow cytometry, it was shown that in vitro treatment of blood cells from beta-thalassemic patients with FPP increased the glutathione content of red blood cells (RBC), platelets and polymorphonuclear (PMN) leukocytes, and reduced their reactive oxygen species, membrane lipid peroxidation and externalization of phosphatidylserine. These effects result in (a) reduced thalassemic RBC sensitivity to hemolysis and phagocytosis by macrophages; (b) improved PMN ability to generate oxidative burst - an intracellular mechanism of bacteriolysis, and (c) reduced platelet tendency to undergo activation, as reflected by fewer platelets carrying external phosphatidylserine. Oral administration of FPP to beta-thalassemic mice (50 mg/mouse/day for 3 months) and to patients (3 g x 3 times/day for 3 months), reduced all the above mentioned parameters of oxidative stress (p < 0.001 in mice and p < 0.005 in patients). These results suggest that FPP, as a potent antioxidant, might alleviate symptoms associated with oxidative stress in severe forms of thalassemia. Copyright (C) 2008 John Wiley & Sons, Ltd.
引用
收藏
页码:820 / 828
页数:9
相关论文
共 39 条
[1]   Flow cytometric measurement of reactive oxygen species production by normal and thalassaemic red blood cells [J].
Amer, J ;
Goldfarb, A ;
Fibach, E .
EUROPEAN JOURNAL OF HAEMATOLOGY, 2003, 70 (02) :84-90
[2]   Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants [J].
Amer, J ;
Ghoti, H ;
Rachmilewitz, E ;
Koren, A ;
Levin, C ;
Fibach, E .
BRITISH JOURNAL OF HAEMATOLOGY, 2006, 132 (01) :108-113
[3]   Chronic oxidative stress reduces the respiratory burst response of neutrophils from beta-thalassaemia patients [J].
Amer, J ;
Fibach, E .
BRITISH JOURNAL OF HAEMATOLOGY, 2005, 129 (03) :435-441
[4]   Oxidative status of platelets in normal and thalassemic blood [J].
Amer, J ;
Fibach, E .
THROMBOSIS AND HAEMOSTASIS, 2004, 92 (05) :1052-1059
[5]   Flow cytometric analysis of the oxidative status of normal and thalassemic red blood cells [J].
Amer, J ;
Goldfarb, A ;
Fibach, E .
CYTOMETRY PART A, 2004, 60A (01) :73-80
[6]   Molecular effects of fermented papaya preparation on oxidative damage, MAP Kinase activation and modulation of the benzo[a]pyrene mediated genotoxicity [J].
Aruoma, Okezie I. ;
Colognato, Renato ;
Fontana, Ilaria ;
Gartlon, Joanne ;
Migliore, Lucia ;
Koike, Keiko ;
Coecke, Sandra ;
Lamy, Evelyn ;
Mersch-Sundermann, Volker ;
Laurenza, Incoronata ;
Benzi, Luca ;
Yoshino, Fumihiko ;
Kobayashi, Kyo ;
Lee, Masaichi-Chang-Il .
BIOFACTORS, 2006, 26 (02) :147-159
[7]   Hypercoagulability in sickle cell disease: A curious paradox [J].
Ataga, KI ;
Orringer, EP .
AMERICAN JOURNAL OF MEDICINE, 2003, 115 (09) :721-728
[8]  
BASS DA, 1983, J IMMUNOL, V130, P1910
[9]   Haemolysis caused by alterations of α- and β-spectrin after 10 to 35 min of severe exercise [J].
Beneke, R ;
Bihn, D ;
Hütler, M ;
Leithäuser, RM .
EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY, 2005, 95 (04) :307-312
[10]   PLATELET ACTIVATION [J].
BLOCKMANS, D ;
DECKMYN, H ;
VERMYLEN, J .
BLOOD REVIEWS, 1995, 9 (03) :143-156