RESULTS Meta- analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities , but not PON1 protein concentration .
The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose , treatment duration and changes in plasma low-density lipoprotein cholesterol concentration .
CONCLUSION The increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes
BACKGROUND Decreased activity of the enzyme paraoxonase-1 ( PON1 ) has been demonstrated in cardiovascular diseases .
Statins , the forefront of pharmacotherapy for dyslipidemia , have been shown to enhance PON1 activity but clinical findings have not been conclusive .
OBJECTIVE To systematic ally review the clinical findings on the impact of statin therapy on PON1 status ( protein concentrations and activities of paraoxonase and arylesterase ) and calculate an effect size for the mentioned effects through meta- analysis of available data .
Modulating effect of atorvastatin on paraoxonase 1 activity in type 2 diabetic Egyptian patients with or without nephropathy.
The aim of this study was to investigate the modulating effect of atorvastatin on serum paraoxonase 1 enzyme ( PON1 ) activity in type 2 diabetic Egyptian patients with or without nephropathy . The present study was carried out on the following groups : control group , which consisted of 30 healthy persons ; Group I , which consisted of 20 type 2 diabetic patients without nephropathy ; and Group II , which consisted of 20 type 2 diabetic patients with nephropathy . All the patients selected were under an antidiabetic regimen of insulin  , and patients receiving antihypertensive agents were excluded from the follow-up study to avoid drug interaction fallacies . Twenty-two patients ( 15 without nephropathy and seven with nephropathy ) received atorvastatin in individually adjusted oral dosage ( range 10 - 20 mg ) once per day for 12 weeks . All cases were subjected to thorough clinical examination and history taking and measurement of serum levels of PON1 activity , malondialdehyde ( MDA ) , glutathione reductase activity , fasting glucose , total cholesterol , triglycerides , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , urea , and creatinine . Urine sample s were collected for determination of proteinuria . The obtained results showed that PON1 activity and HDL significantly decreased and fasting glucose significantly increased in Group I and Group II when compared to the control group , with significant difference in their levels between Group II and Group I. MDA , total cholesterol , and LDL levels significantly increased and glutathione reductase activity significantly decreased in Group I and Group II when compared to the control group . Urea , creatinine , and proteinuria levels showed significant increase in Group II when compared to the control group and Group I , with nonsignificant difference between control group and Group I. Atorvastatin therapy caused a significant increase in PON1 activity , and serum levels of MDA and glutathione reductase activity were significantly decreased and increased , respectively . Also , total cholesterol , triglyceride and LDL-cholesterol levels were significantly reduced with a significant increase in HDL-cholesterol levels . There was a significant modest reduction in serum urea and creatinine levels as well as in proteinuria level . Fasting glucose level was significantly reduced under the antidiabetic regimen of insulin through the follow-up period . PON1 activity showed a significant negative correlation with glucose and LDL , and a significant positive correlation with HDL in all the studied groups . It could be concluded that atorvastatin with its pleiotropic effects could provide optimal therapeutic intervention to control not only dyslipidemia , but also oxidative stress status with consequent improvement in the course of type 2 diabetes and diabetic nephropathy . More specifically , restoration of PON1 activity by atorvastatin opens a window to investigate other drugs that could provide a new adjuvant therapeutic line for better control of diabetes and diabetic nephropathy . Further research is also recommended to study the distribution of PON1 genetic polymorphism among the Egyptian population to explain the variability in its activity and its relationship with other factors that associate diabetes and its complications
RESULTS Meta- analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities , but not PON1 protein concentration .
The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose , treatment duration and changes in plasma low-density lipoprotein cholesterol concentration .
CONCLUSION The increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes
BACKGROUND Decreased activity of the enzyme paraoxonase-1 ( PON1 ) has been demonstrated in cardiovascular diseases .
Statins , the forefront of pharmacotherapy for dyslipidemia , have been shown to enhance PON1 activity but clinical findings have not been conclusive .
OBJECTIVE To systematic ally review the clinical findings on the impact of statin therapy on PON1 status ( protein concentrations and activities of paraoxonase and arylesterase ) and calculate an effect size for the mentioned effects through meta- analysis of available data .