PARTIAL PROTECTION OF ANTIOXIDANTS IN THE MURINE MODEL OF HEMOLYTIC UREMIC SYNDROME (HUS)

GÓMEZ, SONIA; FERNÁNDEZ, GABRIELA; CAMERANO, GABRIELA VERÓNICA; RAMOS, MARÍA VICTORIA; DRAN, GRACIELA; PALERMO, MARINA

Cordoba

Congreso; VII Latin American Congress of Immunology; 2005

HUS is caused by Shiga toxin (Stx2) producing Escherichia coli. Endothelial damage is the hallmark of HUS, caused by Stx2-toxicity and the inflammatory host response, particularly by reactive oxygen intermediates (ROI) produced by activated neutrophils. We previously found ROI-production enhanced in vivo after Stx2 treatment. Antioxidants (N-Acetyl-L-Cysteine, NAC, S-Ethyl-L-Cysteine, ETH) are scavengers of oxidative stress. This study assesses the impact of NAC and ETH administration on survival (%SV) and tissue damage (uremia determinations and histopathology) in mice treated with Stx2. Balb/c mice were dosed with NAC or ETH solutions (1mg/ml) in the drinking water either -48, 0 or +24 h before or after a lethal iv dose of Stx2 (0h) and until the end of the experiment. There were no significant differences in the %SV of mice treated with NAC or ETH +24h after Stx2. However, plasma urea, was found significantly lower in Stx2+NAC compared with Stx2 (12712 mg% vs. 2007 mg%, p0.001. n=12). Survival was increased when NAC or ETH were given at 0h (Stx2: 9%, Stx2+NAC: 26%, p0.05; Stx2+ETH: 58, p0.01, n=24) or -48h (Stx2: 13%, Stx2+NAC: 34%, p0.01; Stx2+ETH: 53, p0.01, n=24). Uremia levels were significantly lower for both time periods and both antioxidants compared with the control. In this study, oral NAC or ETH administration result in partial protection and reduced renal damage in mice treated with Stx2.