Serum Paraoxonase Activity: A New Additional Test for the Improved Evaluation of Chronic Liver Damage

Abstract

Background: Paraoxonase 1 (PON1) is an ester hydrolase present in serum and in the liver. The aims of the present study were to investigate the following: (a) the relationship between serum PON1 activity alterations and the degree of liver damage in patients with chronic liver disease; (b) the influence of genetic variability on serum PON1 activity; and (c) the efficacy of serum PON1 activity measurement, alone and in combination with standard liver function tests, in the assessment of liver damage. Methods: We studied 68 patients with liver cirrhosis, 107 patients with chronic hepatitis, and 368 apparently healthy volunteers. Baseline and salt-stimulated PON1 activities were measured by the hydrolysis of paraoxon. PON1 genotyping at positions 55 and 192 was analyzed by PCR and restriction isotyping. Results: Baseline and stimulated PON1 activities were decreased (P <0.001) in chronic hepatitis and in liver cirrhosis. PON1 activity was significantly correlated with serum total proteins, albumin, and bilirubin in patients but not in controls. There were no significant differences with respect to allele and genotype frequencies between patients and controls. The combination of baseline serum PON1 with five standard biochemical tests had a higher classification accuracy (94% of patients; 96% of controls) than the five standard tests alone (75% of patients; 96% of controls). ROC plots demonstrated a high diagnostic accuracy for baseline serum PON1 [area under the curve, 0.89 (95% confidence interval, 0.86–0.93) in chronic hepatitis and 0.96 (95% confidence interval, 0.94–0.99) in cirrhosis]. Baseline PON1 provided the highest ROC area for cirrhosis vs controls. Conclusions: The significant decrease of PON1 activity in chronic liver diseases is related to the degree of hepatic dysfunction and not to allelic or genotypic differences. Addition of serum PON1 activity measurement to the current battery of tests may improve the evaluation of chronic liver diseases.

Paraoxonase (PON) 1, 2 and 3 Expression in Granulosa Cells and PON1 Activity in Follicular Fluid of Dairy Cows

“…The paraoxonase (PON) gene family in mammals includes three members: PON1, PON2 and PON3 (Aviram and Rosenblat 2004). PON1 is found in serum and is produced primarily in the liver (Ferre et al 2002).…”

Downregulation of human paraoxonase 1 (PON1) by organophosphate pesticides in HepG2 cells

“…In addition, epidemiological studies have reported that the serum concentration of PON1 across the general population is highly variable (can vary by 40-fold) (Brophy et al, 2002). PON1 activity is decreased in several pathological conditions (diabetes type II, coronary heart disease, rheumatoid arthritis, hyperthyroidism, Alzheimer, and others), as well as in workers exposed to OPs independently or have a PON1 genetic polymorphism (Mackness et al, 1998;Brophy et al, 2002;Ferr e et al, 2002;Paragh et al, 2002;Tanimoto et al, 2003;Deakin and James, 2004;Costa et al, 2005;S€ ozmen et al, 2007;Araoud et al, 2010;Hofmann et al, 2010;Gbandjaba et al, 2012;Gugliucci et al, 2012;Gungor et al, 2013). In this sense, Younis et al (2014) reported that circulating IL-6, MCP-1 and PON1 levels are influenced by ovarian stimulation.…”

Serum paraoxonase and arylesterase activities for the evaluation of patients with chronic hepatitis

“…Paraoxonase and arylesterase activities have been shown to be decreased in several liver diseases including liver cirrhosis, CVH (16,17) and non-alcoholic steatohepatitis (35). Kilic et al (17) suggested that low PON1 and arylesterase activity may contribute to the increased liver dysfunction in CH patients by reducing the ability of HDL to retard LDL oxidation and might be clinically useful for monitoring the disease of CH.…”

“…Kilic et al (17) suggested that low PON1 and arylesterase activity may contribute to the increased liver dysfunction in CH patients by reducing the ability of HDL to retard LDL oxidation and might be clinically useful for monitoring the disease of CH. Ferre et al (16) observed that the significant decrease of PON1 activity in chronic liver diseases is related to the degree of hepatic dysfunction. In accordance with the previous studies, especially study of Ferre et al (16), in the present study, we also observed a significant decrease in both arylesterase and paraoxonase activities in CH patients.…”

“…Ferre et al (16) observed that the significant decrease of PON1 activity in chronic liver diseases is related to the degree of hepatic dysfunction. In accordance with the previous studies, especially study of Ferre et al (16), in the present study, we also observed a significant decrease in both arylesterase and paraoxonase activities in CH patients. Recently, Ferre et al (18) investigated PON1 activity and its correlation with oxidative stress, fibrosis and fatty acid synthase (FAS) expression in chronic liver diseases mostly because of hepatitis C. They suggested an active role of PON1 in the regulation of oxidative stress, fibrosis and hepatic cell apoptosis in chronic liver diseases.…”