The oxidative stress induced in vivo by S higa toxin‐2 contributes to the pathogenicity of haemolytic uraemic syndrome

Summary Typical haemolytic uraemic syndrome ( HUS ) is caused by S higa toxin ( S tx)‐producing E scherichia 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. S tx toxicity and the acute inflammatory response raised by the host determine the development of HUS . At present there is no specific therapy to control S tx 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 S tx 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 S tx toxicity. We demonstrated that S tx 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 S tx intoxication. All these parameters were ameliorated by anti‐oxidants reducing platelet activation, renal damage and increasing survival. To conclude, S tx generates a pro‐oxidative state that contributes to kidney failure, and exogenous anti‐oxidants could be beneficial to counteract this pathogenic pathway.