|
|
Previous Article | Table of Contents | Next Article 
Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4307-4313
Formation of Dense Erythrocytes in SAD Mice Exposed to Chronic Hypoxia:
Evaluation of Different Therapeutic Regimens and of a Combination
of Oral Clotrimazole and Magnesium Therapies
Lucia De Franceschi,
Carlo Brugnara,
Philippe Rouyer-Fessard,
Helene Jouault, and
Yves Beuzard
From the Department of Internal Medicine, University of Verona,
Verona, Italy; the Experimental Laboratory of Gene Therapy, Hopital St
Louis, Paris, France; the Laboratory of Hematology, INSERM U91, Hopital
Henri Mondor, Creteil, France; and the Departments of Laboratory
Medicine and Pathology, Children's Hospital, Harvard Medical School,
Boston, MA.
We have examined the effect of hydroxyurea (HU), clotrimazole (CLT),
magnesium oxide (Mg), and combined CLT+Mg therapies on the
erythrocyte characteristics and their response to chronic hypoxia in a
transgenic sickle mouse (SAD) model. SAD mice were treated for 21 days
with 1 of the following regimens (administered by gavage): control
(n = 6), HU (200 mg/d; n = 6), CLT (80 mg/kg/d, n = 5),
Mg (1,000 mg/kg/d, n = 5), and CLT+Mg (80 and 1,000 mg/kg/d, respectively, n = 6). Nine normal mice were also treated as controls (n = 3), HU (n = 3), and CLT+Mg (n = 3). Treatment with HU
induced a significant increase in mean corpuscular volume and cell K
content and a decrease in density in SAD mice. Treatment with the CLT and Mg, either alone or in combination, also increased cell K and
reduced density in SAD mice. After 21 days of treatment, the animals
were exposed to hypoxia (48 hours at 8% O2) maintaining the same treatment. In the SAD mice, hypoxia induced significant cell
dehydration. These hypoxia-induced changes were blunted in either HU-
or Mg-treated SAD mice and were completely abolished by either CLT or
CLT+Mg treatment, suggesting a major role for the Gardos channel in
hypoxia-induced dehydration in vivo.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
A. Rivera
Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor antagonists
Am J Physiol Cell Physiol,
September 1, 2007;
293(3):
C960 - C966.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. de Franceschi, G. Malpeli, A. Scarpa, A. Janin, E. M. Muchitsch, P. Roncada, C. Leboeuf, R. Corrocher, Y. Beuzard, and C. Brugnara
Protective effects of S-nitrosoalbumin on lung injury induced by hypoxia-reoxygenation in mouse model of sickle cell disease
Am J Physiol Lung Cell Mol Physiol,
September 1, 2006;
291(3):
L457 - L465.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Rivera, A. Ferreira, D. Bertoni, J. R. Romero, and C. Brugnara
Abnormal regulation of Mg2+ transport via Na/Mg exchanger in sickle erythrocytes
Blood,
January 1, 2005;
105(1):
382 - 386.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. H. Joiner, R. K. Rettig, M. Jiang, and R. S. Franco
KCl cotransport mediates abnormal sulfhydryl-dependent volume regulation in sickle reticulocytes
Blood,
November 1, 2004;
104(9):
2954 - 2960.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. de Franceschi, A. Baron, A. Scarpa, C. Adrie, A. Janin, S. Barbi, J. Kister, P. Rouyer-Fessard, R. Corrocher, P. Leboulch, et al.
Inhaled nitric oxide protects transgenic SAD mice from sickle cell disease-specific lung injury induced by hypoxia/reoxygenation
Blood,
August 1, 2003;
102(3):
1087 - 1096.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. W. Stocker, L. De Franceschi, G. A. McNaughton-Smith, R. Corrocher, Y. Beuzard, and C. Brugnara
ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice
Blood,
March 15, 2003;
101(6):
2412 - 2418.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Bennekou, L. de Franceschi, O. Pedersen, L. Lian, T. Asakura, G. Evans, C. Brugnara, and P. Christophersen
Treatment with NS3623, a novel Cl-conductance blocker, ameliorates erythrocyte dehydration in transgenic SAD mice: a possible new therapeutic approach for sickle cell disease
Blood,
March 1, 2001;
97(5):
1451 - 1457.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|