Renal effects of Shiga toxin type 2 in pregnant and non-pregnant female rats.

FISHER SIGEL LILIANA KARINA; SACERDOTI FLAVIA; ARAOZ ALICIA; SANCHEZ DIANA; IBARRA CRISTINA; ZOTTA ELSA; SILBERSTEIN CLAUDIA

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica.; 2019

Sociedad Argentina de Investigación Clínica

Shiga toxin-producing Escherichia coli cause acute renal failure and Hemolytic Uremic Syndrome. Previous studies showed that Shiga toxin type 2 (Stx2) intraperitoneally (i.p.) injected in rats during the early gestation period produces kidney damage. After a renal injury, tubular epithelial cells have the capacity of proliferate and repair. The aim of the work was to study the effects of Stx2 on damage and tubular proliferation in kidneys of pregnant rats during the early gestation period, and compare with non-pregnant rats. Pregnant Sprague-Dawley rats, at the eighth day of gestation, were inoculated ip with a sublethal dose of Stx2 (PS) (0.5 ng/g body weight) or diluent (PC). Non-pregnant rats were injected with the same dose of Stx2 (NPS) or diluent (NPC). Rats were placed in metabolic cages, urine samples were collected, and rats were euthanized 1 to 4 days post-injection (dpi). The kidneys were removed for histopathological observations and Ki67 expression, as proliferation marker, was evaluated by immunofluorescence. Tubular necrosis was observed in renal cortex of PS and NPS rats from 2 dpi, which increased significantly at 4 dpi, with respect to PC and NPC rats (p<0.05). Medullar tubules of both NPS and PS did not show significant necrosis. However, a significant increase in Ki67 expression was observed in tubular cells of renal medulla of NPS (8.0 ± 2.0 %) and PS (6.4 ± 0.4 %) with respect to NPC (0.7 ± 0.6 %) and PC (0.7 ± 0.1 %) (n= 4, p<0.05), indicating an increase in medullar and not cortical tubular proliferation. NPS showed a significant increase in urinary flow compared to NPC (36.2 ± 2.6 ml/d vs. 17.0 ± 3.5 ml/d) that was not observed in pregnant rats. Our results showed a similar increase in tubular proliferation in renal medulla of NPS and PS rats. We propose that Stx2 may produce a milder damage in medulla than in cortex, allowing proliferation and repair of the tubular epithelium.