MITOCHONDRIA TARGETED ANTIOXIDANTS AND ORGAN FAILURE. (RESUBMISSION OF 23370)

Mitochondria targeted antioxidants and organ failure

Organ failure as a result of severe infection (sepsis) is the main cause of death in intensive care units. About 2 million patients worldwide develop sepsis every year and the numbers of deaths is similar to the number of deaths from heart attacks. The precise reason why organ damage occurs is not known, but we think that sepsis causes the release of toxic chemicals which damage the energy producing systems of cells (mitochondria), eventually stopping organs from working properly. The body has its own defences against the toxic chemicals, called antioxidants, but they become overwhelmed during sepsis. Our study will test whether antioxidants which preferentially protect mitochondria can protect against organ damage. We need to test the antioxidants in rats first before they can be used in patients with sepsis. Rats will be anaesthetised and injected with bacterial proteins which cause organ failure. We will then treat the rats with antioxidants which have been modified to make them accumulate in mitochondria. After 6 hours we will measure markers of organ function and assess any damage to mitochondria to see if the antioxidants are protective. The proposed project could lead to the development of a novel treatment for patients with sepsis and could potentially save thousands of lives.