Low Paraoxonase 1 Activity Predicts Mortality in Surgical Patients with Sepsis

Suzana Bojic,Sanja Simic-Ogrizovic,Jelena Kotur-Stevuljevic,Zorana Jelic-Ivanovic,Marina Stojanovic,Nevena Kalezic,Aleksandra Stefanovic,Ivan Palibrk,Lidija Memon,Zdravko Kalaba

doi:10.1155/2014/427378

Abstract

Introduction. State of severe oxidative stress is encountered in sepsis. Paraoxonase 1 (PON1) protects against oxidative stress but also undergoes inactivation upon that condition. We investigated PON1 activity in surgical patients with sepsis in relation to oxidative stress status, inflammation, disease severity, and survival. Methods. Prospective observational study. Sixty-nine surgical patients with sepsis were compared to 69 age/sex matched healthy controls. PON1 paraoxonase and diazoxonase activities, selected biochemical, hematological and oxidative stress parameters were measured on admission to ICU and 24, 48, 72, and 96 hours later. Disease severity scores were calculated daily. Results. Septic patients had significantly lower PON1 activities compared to control group at all time points. PON1 activities had good capacity to differentiate septic patients from healthy controls. Low PON1 activities were associated with higher disease severity scores and higher risk of death. Correlation between PON1 activity and markers of inflammation failed to reach significance. Decrease in PON1 activity was correlated with an increase in reducing components in plasma. Conclusion. Our study demonstrated lower PON1 activity in surgical patients with sepsis compared to healthy controls. PON1 activity also reflected severity of the disease. Low PON1 activity was associated with higher mortality of surgical patients with sepsis.

Highlights

State of severe oxidative stress is encountered in sepsis
Our study demonstrated lower Paraoxonase 1 (PON1) activity in surgical patients with sepsis compared to healthy controls
State of exacerbated oxidative stress was evidenced through significantly higher total oxidant status (TOS), prooxidant-antioxidant balance (PAB), and MDA levels and lower Total antioxidant status (TAS) levels compared to the control group

Summary

Introduction

State of severe oxidative stress is encountered in sepsis. We investigated PON1 activity in surgical patients with sepsis in relation to oxidative stress status, inflammation, disease severity, and survival. Our study demonstrated lower PON1 activity in surgical patients with sepsis compared to healthy controls. Low PON1 activity was associated with higher mortality of surgical patients with sepsis. Immune response in sepsis increases production of reactive oxygen and nitrogen species [1] If production of these reactive species exceeds organism’s ability to detoxify the reactive intermediates or to repair the resulting damage, a state of oxidative stress occurs. PON1 peroxidase and esterase activities seem to be of major importance in detoxifying oxidative stress mediators which probably explains the antioxidant and anti-inflammatory potential of the enzyme [4]. No data have been reported on the utility of serial PON1 measurement in surgical patients with sepsis

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