ABSTRACT
Paraoxonase 1 (PON1) has been proposed as an antioxidant enzyme. Although lead-inhibited PON1 activity has been demonstrated mostly based on in vitro experiments, it is uncertain whether this phenomenon is relevant in pathogenesis of lead-induced oxidative stress in the lead exposure. We examined associations of blood lead levels (BLL) and PON1 activity along with oxidative stress parameters in lead exposure workers. We determined malondialdehyde (MDA), conjugated diene (CD), total peroxides (TP), total antioxidant status (TAS), the oxidative stress index (OSI), and PON1 activity in earthenware factory workers (n = 60) and control subjects (n = 65). The lead-exposed group significantly increased lipid peroxidation parameters and OSI compared to the control group (p < 0.001). The lead-exposed group had significantly decreased PON1 activity and TAS levels compared to the control group (p < 0.001). Multiple linear regression analysis revealed that BLL were significantly correlated with decreased TAS (r = -0.496) and PON1 activity (r = -0.434), but with increased CD (r = 0.694), TP (r = 0.614), MDA (r = 0.788), and OSI (r = 0.722). Interestingly, BLL at 10 µg/dL significantly decreased PON1 activity and increased oxidative stress parameters with insignificant changes in other biochemical and hematological parameters. Altogether, the reduction of PON1 activity may associate in an imbalance in pro-oxidants and antioxidants, leading to oxidative damage in lead-exposed workers even at low BLL.
Subject(s)
Aryldialkylphosphatase/blood , Industry , Lead/blood , Occupational Exposure , Oxidative Stress/drug effects , Adult , Case-Control Studies , Female , Humans , Lead/toxicity , Lipid Peroxidation/drug effects , Male , Occupational Exposure/adverse effects , Occupational Exposure/analysis , ThailandABSTRACT
It has been proposed that paraoxonase1 (PON1), a high density lipoprotein (HDL)-associated esterase/lactonase, has anti-atherosclerotic properties. The activity of PON1 is influenced by PON1 polymorphisms. However, the influence of PON1 polymorphisms on PON1 activity and oxidative stress in response to lipid-lowering drugs remains poorly understood. The objective of the present study was to investigate the effects of atorvastatin on PON1 activity and oxidative status. The influence of PON1 polymorphisms on PON1 activity and oxidative status in response to atorvastatin treatment was also evaluated. In total, 22 hypercholesterolemic patients were treated with atorvastatin at a dose of 10 mg/day for 3 months. Lipid profile, lipid oxidation markers (malondialdehyde (MDA), conjugated diene (CD), total peroxides (TP)), total antioxidant substance (TAS), oxidative stress index (OSI), and paraoxonase1 activity were determined before and after treatment. L55M, Q192R, and T(-107)C PON1 polymorphisms were also determined. Atorvastatin treatment significantly reduced the levels of total cholesterol (24.5%), low density lipoprotein (LDL) cholesterol (25.4%), triglycerides (24.4%), CD (4.4%), MDA (15.2%), TP (13.0%) and OSI (24.0%), and significantly increased the levels of TAS (27.3%), and PON1 activity (14.0%). Interestingly, the increase in PON1 activity and the reduction in oxidative stress in response to atorvastatin were influenced only by the PON1 T-107C polymorphism. Atorvastatin treatment improved the lipid profile, lipid oxidation, and oxidative/antioxidative status markers including the activity of PON1 towards paraoxon. These beneficial effects may be attributed to the antioxidant properties of statins and the increase in PON1 activity. The increase in PON1 activity was enhanced by the PON1 T-107C polymorphism.
Subject(s)
Anticholesteremic Agents/pharmacology , Aryldialkylphosphatase/drug effects , Heptanoic Acids/pharmacology , Hypercholesterolemia/drug therapy , Pyrroles/pharmacology , Aryldialkylphosphatase/genetics , Aryldialkylphosphatase/metabolism , Atorvastatin , Humans , Hypercholesterolemia/physiopathology , Lipid Peroxidation/drug effects , Lipids/blood , Middle Aged , Oxidative Stress/drug effects , Paraoxon/metabolism , Polymorphism, GeneticABSTRACT
OBJECTIVE: To determine the PON1 activity and phenotype distribution in a Thai population. STUDY DESIGN: Prospective Descriptive study. MATERIAL AND METHOD: Between October 2001 and April 2002, 160 healthy Thai individuals aged 20-74 years were assessed for PON1 activity and the phenotype distribution by using dual substrate method. RESULTS: The means +/- SD of basal, salt-stimulated paraoxonase and arylesterase activities were 239.7 +/- 83.9 nmol/min/mL 555.2 +/- 222.2 nmol/min/mL and 147.6 +/- 33.8 micromol/min/mL respectively. The authors observed a wide interindividual variability up to 6.9-fold for paraoxonase activity and 4.6-fold for arylesterase activity. The authors found a range of ssPON/ARE ratio from 1.04 to 7.05 and three distinctive phenotype modals of AA (1.04-2.25), AB (2.44-4.29), and BB (4.53-7.05) with frequencies of 14.4% (AA), 51.9% (AB), and 33.7% (BB). The authors also observed the association of sex with lipid parameters and PON1 activity. CONCLUSION: The distribution of PON1 phenotype in Thais is clearly trimodal with high frequency in BB phenotype.
