Cardiovascular Insufficiency, Abdominal Sepsis, and Patients’ Age Are Associated with Decreased Paraoxonase-1 (PON1) Activity in Critically Ill Patients with Multiple Organ Dysfunction Syndrome (MODS)

Abstract

Oxidative stress and uncontrolled inflammation are hallmarks of sepsis, leading to organ failure and death. As demonstrated in animal studies, oxidative stress can be alleviated by antioxidant therapies. Paraoxonase-1 (PON1) is a serum-based antioxidant, anti-inflammatory agent, detoxifier, and quorum-sensing factor found to be a prognostic marker in sepsis. However, its associations with multiple organ dysfunction syndrome (MODS), a complication of sepsis and the leading cause of death in the surgical intensive care units (ICU), as well as with specific organ dysfunction, infection site, and invading pathogen remain unknown. Therefore, we measured arylesterase activity of PON1 in 87 individuals (35 with MODS) and related it to the clinical type, organ failure, infection site, pathogens, and hematological and biochemical indices of inflammation at admission to ICU and during a five-day follow-up. Suitability of PON1 and its indices derived from a follow-up as biomarkers in MODS was evaluated as well. MODS was associated with decreased PON1, more so in patients with septic shock, displaying an excellent accuracy as a marker of MODS (91%) and a fair one as a marker in differentiating septic shock from severe sepsis (76%). Decreased admission PON1 accompanied cardiovascular insufficiency (CVI), and, as its marker, PON1 displayed a good accuracy (82%). It was also associated with the abdomen as a site of infection but not with an invading pathogen. In multivariate analysis, 50% of variability in PON1 activity in patients with MODS was explained by the patients’ age, CVI, and abdomen as a site of infection. Patients with septic shock, CVI, and abdominal MODS had distinctly different dynamics of PON1 during a follow-up. Mean PON1 activity during the follow-up reflected the associations observed for admission PON1 but was also significantly associated with metabolic dysfunction. Our results show PON1 potential as a biomarker in MODS, particularly as an indicator of CVI.

Arylesterase Activity of HDL Associated Paraoxonase as a Potential Prognostic Marker in Patients With Sepsis and Septic Shock—A Prospective Pilot Study

“…In a small study including ten patients in-and outside the ICU, septic patients had reduced CEC, but the activity of PON1 was not significantly different (16). A recent report showed that activity of PON1 was a good marker for the development of multiorgan dysfunction syndrome (46). Novak et al (47) showed a non-significant trend of lower AEA in non-survivors of sepsis.…”

Potential Predictive Value of Serum Pentraxin 3 and Paraoxonase 1 for Cardiometabolic Disorders Development in Patients with Psoriasis—Preliminary Data

“…It was also observed that decreased PON1 activity was related to the increased occurrence of atherogenic dyslipidemia [ 30 ]. Bednarz-Misa et al noted a significantly decreased PON1 level among patients that were admitted to the intensive care unit with multiple organ disfunction syndrome (MODS) and reported that lower PON1 activity was associated with cardiovascular insufficiency [ 31 ]. Moreover, Bednarz-Misa et al suggested that PON1 could be used as a marker of cardiovascular insufficiency with an accuracy of 82% [ 31 ].…”

Arlyesterase activity of Paraoxonase-1 enzyme in Iraqi patients with β-thalassemia minor

“…It has been found that PON1 exhibits activity of arylesterase (ARE) (aromatic carboxylic acid esters hydrolysis), lactonase (lactones hydrolysis), and paraoxonase (organophosphatase hydrolysis) [15][16][17] . These activities are described as one of PON1 physiological functions as well as the antioxidant activity which is considered another biological role of PON1 [18,19] . It was also demonstrated that more than 95% of the PON1 in serum exhibits ARE activity (ARE-PON1) as in vitro investigated by controlling phenylacetate hydrolysis [16] .…”