Ciprofibrate increases paraoxonase activity in patients with metabolic syndrome

Abstract

Aims Diabetic dyslipidaemia with decreased high‐density lipoprotein‐cholesterol (HDL‐C) concentration plays a key role in enhanced atherosclerosis. The antioxidant effect of HDL is due to the influence of human paraoxonase 1 (PON1) and several authors have described decreased activity of this enzyme in Type 2 diabetics and subjects with metabolic syndrome. The goal of this study was to examine the effect of daily ciprofibrate on serum PON1 and lipoprotein concentrations in patients with metabolic syndrome. Methods Fifty‐one patients with metabolic syndrome were enrolled into the study. We examined the effect of 100 mg day−1 ciprofibrate treatment on lipid concentrations, oxidized low‐density lipoprotein (LDL), PON1 concentrations and activity. We also investigated the calculated size of LDL‐cholesterol (LDL‐C). Results During the 3‐month study, it was observed that following treatment with ciprofibrate, the serum triglyceride concentration decreased significantly (from 2.76 ± 0.9 mmol l−1 to 2.27 ± 1.6 mmol l−1; −18%; P < 0.001), while HDL‐C increased significantly (from 0.95 ± 0.2 mmol l−1 to 1.2 ± 0.3 mmol l−1; 26%; P < 0.001). The oxidatively modified LDL‐C concentration decreased significantly (from 137 ± 19 U l−1 to 117 ± 20 U l−1; P < 0.001), while HDL‐associated apolipoprotein A1 significantly increased (from 1.35 ± 0.2 g l−1 to 1.75 ± 0.3 g l−1; P < 0.001). The LDL‐C/LDL‐apoB ratio, which reflects the size of LDL, increased significantly (from 0.96 ± 0.05 to 1.05 ± 0.06; P < 0.05). Serum PON1 activity was significantly elevated (from 108 ± 34 U l−1 to 129 ± 31 U l−1; P < 0.05), while standardized values for HDL‐C remained significantly unchanged (PON1/HDL‐C) (from 114 ± 21 to 107 ± 20; NS). Conclusion Three months of treatment with ciprofibrate favourably affected the lipid profile, increased LDL resistance to oxidation and improved antioxidant status by increasing serum paraoxonase activity in these patients.

Non-diabetic metabolic syndrome and obesity do not affect serum paraoxonase and arylesterase activities but do affect oxidative stress and inflammation

“…Recent studies have shown that PON-1, a protective enzyme for LDL-C oxidation, is an important molecule in the pathogenesis of atherosclerosis (25). PON-1 has been studied in MetS and obesity in several studies in different study groups, and the results of these studies are conflicting (18,(26)(27)(28). Senti et al showed that PON activity is lower in MetS compared to controls, and they suggested that the increased oxidative stress is related with the low PON activity (18).…”

In vitro Effect of Ciprofibrate on Human Carbonic Anhydrase II and Glucose 6-Phosphate Dehydrogenase Activities

“…reported that ciprofibrate increased paraoxonase activity in patients with metabolic syndrome [26]. The enzymespecific effect of ciprofibrate on 3-hydroxy steroid dehydrogenase-isomerase (3-HSD) in the testes, a tissuespecific effect, was also evident since no significant effects of ciprofibrate were reported in the activities of 3-HSD or Steroid 21-hydroxylase (21-OHase) in the adrenal glands of the same animals [27].…”

“…Numerous in vitro and in vivo studies have investigated the effect of ciprofibrate on enzyme activities [24][25][26][27]. Goll et al applied ciprofibrate and its species at varying concentrations (100-500 mM) to rat hepatocyte culture for 72 hours and reported an increase in the activities of mitochondrial enzymes (acyl CoA oxidase (ACO) and carnitine acetyl transferase (CAT)) [24].…”

Synthesis and evaluation of novel 2-[(1,2,4-triazol-3-yl)thio]acetamide derivatives as potential serum paraoxonase-1 (PON1) activators

“…Experimental animal studies support the clinical evidence of the stimulatory effects of lipid-lowering activity of drug therapy [22]. Fibrate group of drugs gemfibrozil, fenofibrate and ciprofibrate ( Figure 1) were found to increase the serum PON activity [23][24][25][26]. In patients with coronary disease, lowdose aspirin increases ~ 13% of serum PON1 activity [27], but in healthy volunteers it was found not to increase the activity [28].…”