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Critical Care  2013 

Compartmentalization of lipid peroxidation in sepsis by multidrug-resistant gram-negative bacteria: experimental and clinical evidence

DOI: 10.1186/cc11930

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Abstract:

Lethal sepsis was induced in rats by the intraperitoneal injection of one MDR isolate of Pseudomonas aeruginosa. Produced malondialdehyde (MDA) was measured in tissues 5 hours after bacterial challenge with the thiobarbiturate assay followed by high-performance liquid chromatography (HPLC) analysis. Results were compared with those from a cohort of patients with ventilator-associated pneumonia (VAP) and sepsis by MDR Gram-negative bacteria. More precisely, serum MDA was measured on 7 consecutive days, and it was correlated with clinical characteristics.MDA of septic rats was greater in the liver, spleen, and aortic wall, and it was lower in the right kidney compared with sham operated-on animals. Findings were confirmed by the studied cohort. Circulating MDA was greater in patients with hepatic dysfunction and acute respiratory distress syndrome (ARDS) compared with patients without any organ failures. The opposite was found for patients with acute renal dysfunction. No differences were found between patients with ARDS without or with cardiovascular (CV) failure and patients without any organ failure. Serial measurements of MDA in serum of patients indicated that levels of MDA were greater in survivors of hepatic dysfunction and ARDS and lower in survivors of acute renal dysfunction.Animal findings and results of human sepsis are complementary, and they suggest a compartmentalization of lipid peroxidation in systemic infections by MDR gram-negative bacteria.Oxidative stress results from an imbalance between production of reactive oxygen and nitrogen species (ROS and RNS) and endogenous antioxidant defense mechanisms [1]. A growing body of evidence suggests that many of the effects of cellular dysfunction under oxidative stress are mediated by products of nonenzymatic reactions, such as the peroxidative degradation of polyunsaturated fatty acids. Aldehyde molecules generated during lipid peroxidation are considered ultimate mediators of toxic effects elicited by oxid

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