Oxidation of uric acid and association with Sepsis

• Grant number: 22/06870-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2022
• Effective date (End): December 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Flavia Carla Meotti
• Grantee: Priscilla Davila Mazzuco Alves
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/14898-2 - Investigations of the redox processes in inflammatory response and associated pathologies, AP.JP2

Abstract

Sepsis, a severe infection associated with organ dysfunction, represents the main cause of death in Intensive Care Units (ICU) worldwide. The difficulty of effective treatment is due to the diverse pathogenesis of the disease, which varies depending on the individual characteristics of each patient's response. Therefore, understanding the metabolic and inflammatory status of each patient can make therapeutic measures more assertive. Some studies have shown a positive correlation between plasma uric acid levels and a worse prognosis in sepsis. In this sense, a possible mechanism is that the uric acid can cause endothelial damage, an important condition in sepsis. However, the association between uric acid and sepsis is not always independent of kidney damage. Our research group has demonstrated that uric acid is an important substrate for inflammatory enzymes and the oxidation of uric acid by these enzymes produces highly reactive intermediates such as urate free radical and urate hydroperoxide. The production of these oxidants has been suggested as a key mechanism in endothelial damage caused by uric acid and is potentially involved in the genesis of vascular inflammation and atherosclerosis. Furthermore, oxidation of uric acid by inflammatory enzymes prevented the formation of hypochlorous acid, an important microbicide, and thus decreased the ability of inflammatory cells to contain the growth of Pseudomonas aeruginosa. In this sense, the objective of this project is to identify whether there is a correlation between uric acid oxidation and a worse prognosis in sepsis. Therefore, the levels of uric acid, its final oxidation product allantoin, and oxidation intermediates, which form adducts with albumin in patients admitted to the ICU of Hospital das Clínicas will be compared with routine biochemical and clinical data that inform the inflammatory condition, sepsis and the clinical course of the disease. We believe that, through this study, it will be possible to identify whether uric acid and its oxidation have any contribution to the progression of sepsis. If so, the measurement of uric acid levels, as it is a simple colorimetric assay, may be incorporated into the clinical routine and, from then on, individual therapeutic measures that include the use of uric acid synthesis inhibitors or uricosuric drugs may be considered.(AU)