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Title: Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status
Authors: Amar Nagila
Thinnakorn Permpongpaiboon
Soontharee Tantrarongroj
Pornwalee Porapakkham
Kultira Chinwattana
Sara Deakin
Sureerut Porntadavity
Fishtail Hospital
Huachiew Chalermprakiat University
Mahidol University
Thailand Ministry of Public Health
Hopitaux universitaires de Geneve
Keywords: Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2009
Citation: Pharmacological Reports. Vol.61, No.5 (2009), 892-898
Abstract: It has been proposed that paraoxonasel (PON1), a high density lipoprotein (HDL)-associated esterase/lactonase, has antiatherosclerotic 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 paraoxonasel 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. Copyright © 2009 by Institute of Pharmacology Polish Academy of Sciences.
ISSN: 17341140
Appears in Collections:Scopus 2006-2010

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