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Compartmentalization of lipid peroxidation in sepsis by multidrug-resistant gram-negative bacteria: experimental and
Introduction:
Recent evidence suggests a link between excess lipid peroxidation and specific organ failures in sepsis. No study has been performed in sepsis by multidrug-resistant (MDR) Gram-negative bacteria.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Lipid peroxidation, measured by malondialdehyde (MDA), is compartmentalized in sepsis caused by multidrug-resistant Gram-negative bacteria. MDA levels varied across organs in rats and correlated with specific organ failures in human sepsis patients.
Area of Science:
- Biochemistry
- Pathophysiology
- Microbiology
Background:
- Lipid peroxidation is increasingly linked to organ failure in sepsis.
- No prior studies have investigated this in sepsis caused by multidrug-resistant (MDR) Gram-negative bacteria.
Purpose of the Study:
- To investigate the role and localization of lipid peroxidation in sepsis induced by MDR Gram-negative bacteria.
- To compare findings in an animal model with human sepsis patients.
Main Methods:
- Sepsis was induced in rats using Pseudomonas aeruginosa (MDR isolate).
- Malondialdehyde (MDA) levels were measured in rat tissues and human patient serum using thiobarbiturate assay and HPLC.
- Human data included patients with ventilator-associated pneumonia (VAP) and sepsis; serum MDA was tracked over 7 days.
Main Results:
- Septic rats showed increased MDA in the liver, spleen, and aorta, but decreased MDA in the kidney.
- Human patients with hepatic dysfunction and ARDS had higher serum MDA; those with renal dysfunction had lower MDA.
- MDA levels in survivors indicated different patterns for hepatic/ARDS versus renal dysfunction.
Conclusions:
- Animal and human results suggest compartmentalization of lipid peroxidation during systemic infections by MDR Gram-negative bacteria.
- MDA serves as a potential biomarker for specific organ dysfunction in this context.
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