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Compensatory renal growth protects mice against Shiga toxin 2-induced toxicity

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Abstract

Uninephrectomy (Unx) is followed by the compensatory renal growth (CRG) of the remaining kidney. Previous evidence has shown that during CRG, renal tissue is resistant to a variety of pathologies. We tested the hypothesis that the functional changes that take place during CRG could attenuate Shiga toxin (Stx) toxicity in a mouse model of Stx2-induced hemolytic uremic syndrome (HUS). The participation of nitric oxide (NO) was analyzed. After CRG induction with Unx, mice were exposed to a lethal dose of Stx2, and the degree of renal damage and mortality was measured. Stx2 effects on the growth, renal blood flow (RBF) and NO synthase (NOS) intrarenal expression in the remaining kidney were then studied. The induction of CRG strongly prevented Stx2-mediated mortality and renal damage. Administration of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) during CRG partially impaired the protection. Both Stx2 and L-NAME interfered with the hypertrophic and hyperplastic responses to Unx, as well as with the increase in RBF. In intact mice, Stx2 decreased renal perfusion, inhibited endothelial NOS basal expression and enhanced inducible NOS expression; all of these effects were attenuated by prior Unx. It is concluded that during CRG mice are highly protected against Stx2 toxicity and lethality. The protective capacity of CRG could be related to the enhancement of renal perfusion and preservation of eNOS renal expression, counterbalancing two major pathogenic mechanisms of Stx2.

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Acknowledgements

We thank Dr. Carlos Amorena, University of San Martin Bs. As., for his critical review of the manuscript, and Vet. Hector Costa for excellent technical assistance. This work was supported by grants from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Fundación “Alberto J. Roemmers” and Agencia Nacional de Promoción Científica y Tecnológica, Argentina.

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Authors and Affiliations

  1. Sección Medicina Experimental, Academia Nacional de Medicina, Buenos Aires, Argentina

    Gabriela Verónica Camerano, Oscar David Bustuoabad & Graciela Isabel Dran

  2. Departamento de Patología, Centro de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires, Argentina

    Roberto Pablo Meiss

  3. Sección Inmunología, Academia Nacional de Medicina, Buenos Aires, Argentina

    Sonia Alejandra Gómez, Gabriela Cristina Fernández, Martín Amadeo Isturiz & Marina Sandra Palermo

  4. División Medicina Experimental, ILEX,, Academia Nacional de Medicina, Pacheco de Melo 3081, C1425 AUM, Buenos Aires, Argentina

    Gabriela Verónica Camerano

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  1. Gabriela Verónica Camerano
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  2. Oscar David Bustuoabad
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Correspondence to Gabriela Verónica Camerano.

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Camerano, G.V., Bustuoabad, O.D., Meiss, R.P. et al. Compensatory renal growth protects mice against Shiga toxin 2-induced toxicity. Pediatr Nephrol 21, 1082–1092 (2006). https://doi.org/10.1007/s00467-006-0115-5

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