ABSTRACT
The aim of this study was to investigate modulating effect of atorvastatin on serum paraoxonasel enzyme [PON1] activity in type 2 diabetic Egyptian patients with or without nephropathy. The present study was carried out on the following groups: thirty healthy persons were enrolled as [Control group], group I: twenty type 2 diabetic patients without nephropathy, group II: twenty type 2 diabetic patients with nephropathy. All the patients were selected to be under the antidiabetic regimen by insulin, and patients received antihypertensive agents were excluded from the follow up study to avoid drug interaction fallacies. Twenty two patients [15 without nephropathy and 7 with nephropatuy] received [atorvastatin] in individually adjusted oral dosage [range 10-20 mg] once/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 samples were collected for determination of proteinuria. The obtained results showed that PON1 activity and HDL significantly decreased and fasting glucose significantly increased in patients without [group I] and with nephropathy [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 patients with diabetic nephropathy [group II] when compared to control group and patients without nephropathy [group I], with non significant difference between control group and group I [Atorvastatin] therapy caused significant increase in PON1 activity and serum levels of MDA and glutathione reductase activity were significantly decreased and increased, respectively. Also, total cholesterol, triglycerides and LDL-cholesterol levels were significantly reduced with significant increase in HDL-cholesterol levels. There was significant modest reduction in serum urea and creatinine levels as well as proteinuria level. Fasting glucose level was significantly reduced under the antidiabetic regimen of insulin through the follow up period. PON1 activity showed significant negative correlation with glucose and LDL and significant positive correlation with HDL in the all studied groups. It could be concluded that [atorvastatin] by 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 PONl activity by [atorvastatin] open a window to investigate other drugs that could provide a new adjuvant therapeutic line for more control of diabetes and diabetic nephropathy. Further studies is also recommended to study distribution of PON1 genetic polymorphism among Egyptian population to explain variability in its activity and its relationship with other factors that associate diabetes and its complications