Effects of Shiga toxin 2 in pregnant and non-pregnant female rats

Abstract

Shigatoxin-producing Escherichia colicauses acute renal failure and Hemolytic Uremic Syndrome. It was reported that inhibition of nitric oxide(NO) by Shiga toxin type 2 (Stx2) enhanced renal damage in mice and baboonmodels of Stx-mediated HUS. The aim of the work was to study the evolution ofthe damages caused by Stx2 in P compare with NP rats. Pregnant Sprague-Dawleyrats, at day 8 of gestation, and NP rats were ip inoculated with 0.5 ng Stx2/gbody weight (PS, NPS) or diluent (PC, NPC). Some PS and PC rats were treatedwith 1mg/ml L-NAME, NO inhibitor, in drinking water (PLS, PLC) from 24 h beforeip injection to 4 days post-injection (dpi). Rats were individually housed,checked for water and food intake, and weighted every 24 h until 30 dpi. At 4dpi, blood and 24 h urine samples were collected to determine urinary flow andfree water clearance (CH20). Then, rats were euthanized and kidneyswere removed for histopathological observations. NPS and PS rats showed adecrease in food intake and weight with respect to controls (p<0.05). PSrats increased food intake and recovered weight at 5 dpi, while NPS rats showedan improvement at 14 dpi. The water intake increased in NPS and PS ratscompared to controls until 7 dpi (p<0.05). In NPS at 4 dpi, the rise inwater intake coincided with an increase in urinary flow and CH20respect to NPC (p<0.05), different from what was observed in PS. The renalcortex of NPS presented significantly more necrosis and atrophied tubules thanPS (p<0.05). Preliminary results in PLS rats showed that L-NAMEsignificantly increased renal necrosis compared with PLS and PLC rats (p<0.05).In conclusion, PS rats suffered less renal damage and recovered from the Stx2effect faster than NPS rats. L-NAME increased Stx2 effect in PLS suggesting thatphysiology changes caused by pregnancy, like increasing in NO production, may contributeto protect maternal kidney from Stx2 effects.