INVESTIGADORES
IBARRA cristina Adriana
artículos
Título:
A glucosylceramide synthase inhibitor protects rats against the cytotoxic effects of Shiga toxin-2
Autor/es:
SILBERSTEIN CLAUDIA; LUCERO MARÍA SOLEDAD; ZOTTA ELSA; COPELAND DIANE P; LINGYUN L; REPETTO HORACIO A; IBARRA CRISTINA
Revista:
PEDIATRIC RESEARCH
Editorial:
INT PEDIATRIC RESEARCH FOUNDATION, INC
Referencias:
Lugar: The Woodlands, Texas; Año: 2011 vol. 69 p. 390 - 394
ISSN:
0031-3998
Resumen:
p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0cm 0cm 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; } Post-diarrhea hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children in Argentina. Renal damage has been strongly associated with Shiga toxin (Stx) which binds to the globotriaosylceramide (Gb3) receptor on the plasma membrane of target cells. The purpose of the study was to evaluate the in vivo effects of C-9, a potent inhibitor of glucosylceramide (GL1) synthase and Gb3 synthesis, on kidney and colon in an experimental model of HUS in rats. Rats were intraperitoneal injected (i.p.) with supernatant from recombinant E. coli expressing Stx2 (sStx2). A group of these rats were orally treated with C-9 during 6 days, from 2 days prior to 4 days after sStx2 injection. The injection of sStx2 caused renal damage as well as a loss of goblet cells in colonic mucosa. Oral treatment with C-9 significantly decreased rat mortality to 50% and reduced the extension of renal and intestinal injuries in the surviving rats. The C-9 also decreased Gb3 and GL1 expression levels in rat kidneys. It is particularly interesting that an improvement was seen when C-9 was administered 2 days before challenge, which makes it potentially useful for prophylaxis. @font-face { font-family: "Arial"; }@font-face { font-family: "Times"; }p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0cm 0cm 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; font-weight: bold; }div.Section1 { page: Section1; }ol { margin-bottom: 0cm; }ul { margin-bottom: 0cm; } Cited by Elie Dolgin in News of Nature Medicine volume 17 , number 7, july 2011.