The oxidative stress induced in vivo by Shiga toxin-2 contributes to the pathogenicity of haemolytic uraemic syndrome

Authors

  • S. A. Gomez,

    1. Servicio de Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS ‘Dr Carlos G. Malbrán’, Buenos Aires, Argentina
    Search for more papers by this author
    • These authors contributed equally to this paper.
  • M. J. Abrey-Recalde,

    1. Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX) (CONICET), Buenos Aires, Argentina
    Search for more papers by this author
    • These authors contributed equally to this paper.
  • C. A. Panek,

    1. Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX) (CONICET), Buenos Aires, Argentina
    Search for more papers by this author
  • N. F. Ferrarotti,

    1. Laboratorio de Química General, Departamento de Química Analítica y Fisico- química, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
    Search for more papers by this author
  • M. G. Repetto,

    1. Laboratorio de Química General, Departamento de Química Analítica y Fisico- química, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
    Search for more papers by this author
  • M. P. Mejías,

    1. Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX) (CONICET), Buenos Aires, Argentina
    Search for more papers by this author
  • G. C. Fernández,

    1. Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX) (CONICET), Buenos Aires, Argentina
    Search for more papers by this author
  • S. Vanzulli,

    1. División Patología, Instituto de Investigaciones Oncológicas, Academia Nacional de Medicina, Buenos Aires, Argentina
    Search for more papers by this author
  • M. A. Isturiz,

    1. Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX) (CONICET), Buenos Aires, Argentina
    Search for more papers by this author
  • M. S. Palermo

    Corresponding author
    • Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX) (CONICET), Buenos Aires, Argentina
    Search for more papers by this author

Correspondence: M. S. Palermo, Instituto de Medicina Experimental (IMEX) (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM Buenos Aires, Argentina.

E-mail: mspalermo@hematologia.anm.edu.ar

Summary

Typical haemolytic uraemic syndrome (HUS) is caused by Shiga toxin (Stx)-producing Escherichia coli infections and is characterized by thrombotic microangiopathy that leads to haemolytic anaemia, thrombocytopenia and acute renal failure. Renal or neurological sequelae are consequences of irreversible tissue damage during the acute phase. Stx toxicity and the acute inflammatory response raised by the host determine the development of HUS. At present there is no specific therapy to control Stx damage. The pathogenic role of reactive oxygen species (ROS) on endothelial injury has been largely documented. In this study, we investigated the in-vivo effects of Stx on the oxidative balance and its contribution to the development of HUS in mice. In addition, we analysed the effect of anti-oxidant agents as therapeutic tools to counteract Stx toxicity. We demonstrated that Stx induced an oxidative imbalance, evidenced by renal glutathione depletion and increased lipid membrane peroxidation. The increased ROS production by neutrophils may be one of the major sources of oxidative stress during Stx intoxication. All these parameters were ameliorated by anti-oxidants reducing platelet activation, renal damage and increasing survival. To conclude, Stx generates a pro-oxidative state that contributes to kidney failure, and exogenous anti-oxidants could be beneficial to counteract this pathogenic pathway.

Ancillary