Development of Hemolytic Uremic Syndrome (HUS) model in rats

ZOTTA E, OCHOA F, REPETTO HA, IBARRA C.

Melbourne, Australia

Congreso; VTEC2006 International Symposium and Workshop on Shiga toxin (verocytotoxin)-producing Escherichia coli infections.; 2006

Australian Society for Microbiology

Escherichia coli strains producing Shiga toxins colonize the lower gastrointestinal tract and are associated with watery and bloody diarrhea and HUS. Nevertheless the experimental animal models used until the moment are not resembled totally the HUS described in humans. Acute renal failure with oliguria associated to acute tubular necrosis (ATN) and microangiophatic thrombosis (MAT) was reported in children. The objective of this work was to obtain a model of HUS in rats that simulate the human disease. Thus, Sprague Dawley rats were inoculated by intraperitoneal way with culture supernatant from recombinant E. coli that expresses Stx2 (80ng/mL). After 48 h of treatment, functional and histological studies were made. Physiological studies revealed that creatinine and urea clearance were significantly decreased (p<0.01). Rats developed poliuria at 24 h post inoculation that progressing to oliguria at 48 h. Moreover, the rats presented watery diarrhea. Macroscopic analysis revealed a hyperemic peritoneal face from large intestine and bowel with luminal water accumulation. The kidneys were friable and congestive. Histopathological analysis revealed ATN and MAT in glomerular capillary. Strong vascular congestion in the three levels from intestinal and colonic wall, with extruded erythrocytes in serosa and chorion from interglandular crypts was observed. These areas were the same where Stx2 was detected by immunohistochemestry. In conclusion Stx2 inoculated in peritoneum, developed an acute renal failure with oliguria, MAT and ATN similar to those reported in humans. We described for the first time that Stx2 produce histological changes and developing watery diarrhea when it was inoculated by intraperitoneal way.