European Journal of Endocrinology (2011) 164 219–222 ISSN 0804-4643 CLINICAL STUDY Serum paraoxonase and arylesterase activities in metabolic syndrome in Zahedan, southeast Iran Mohammad Hashemi, Dor Mohammad Kordi-Tamandani1, Nooshin Sharifi1, Abdolkarim Moazeni-Roodi2, Mahmoud-Ali Kaykhaei3, Behzad Narouie3 and Adam Torkmanzehi1 Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan 98167-43175, Iran, 1Department of Biology, Faculty of Sciences, University of Sistan and Baluchestan, Zahedan 98155-987, Iran and 2Research Center for Infectious Diseases and Tropical Medicine and 3Department of Internal Medicine, School of Medicine, Zahedan University of Medical Sciences, Zahedan 98167-43175, Iran (Correspondence should be addressed to M Hashemi; Email: [email protected]) Abstract Objective: Paraoxonase (PON) is associated with high-density lipoprotein and protects serum lipid from oxidation. The aim of this study was to determine serum PON, arylesterase (ARE) activities, and total antioxidant capacity (TAC) in metabolic syndrome (MES). Methods: This case–control study was performed on 106 patients with MES and 231 healthy subjects. Serum PON and ARE activities were determined spectrophotometrically. TAC was determined using ferric reducing ability of plasma assay. Results: The results showed that serum PON activity was significantly lower in patients with MES (69.62G59.86 IU/l) than healthy subjects (91.64G77.45 IU/l) (P!0.05). The serum ARE activity in MES and normal subjects were 45.23G23.24 and 65.69G31.10 kU/l respectively. The ARE activity was significantly lower in patients with MES than normal subjects (P!0.0001). No significant differences were observed between MES and normal subjects regarding TAC. Conclusion: The lower PON and ARE activities in MES may be considered an independent risk factor for cardiovascular disease, which remains to be cleared. European Journal of Endocrinology 164 219–222 Introduction To the best of our knowledge, information regarding PON and ARE activities in MES is limited. The aim of Metabolic syndrome (MES), a collection of cardio- this study was to find out the levels of PON and ARE vascular risk factors including central obesity, hyperten- activities in MES. sion, hyperglycemia, glucose intolerance, and dyslipidemia, is associated with an increased risk of cardiovascular disease and diabetes (1). Human serum paraoxonase 1 (PON1) is w43–45 kDa glycoprotein, Materials and methods synthesized mainly by the liver, which circulates in serum in association with high-density lipoprotein This case–control study was performed on 106 (HDL) and protects low-density lipoprotein (LDL) from individual with MES and 231 normal subjects. The oxidation by the hydrolysis of biologically active demographic and biochemical characteristic of the lipoperoxides (2). The activity of this enzyme is groups are shown in Table 1. measured using paraoxon or is estimated from the The study was approved by the local ethical activity of arylesterase (ARE) using phenyl acetate. committee of Zahedan University of Medical Sciences It has been reported that ARE activity is not affected by and written informed consent was obtained from all the polymorphisms of PON1 (3, 4). subjects. The MES was determined as the presence of Serum PON1 activity was found to be reduced in a three or more of five components according to the number of pathological conditions including coronary national cholesterol education program (NCEP) ATP III artery disease (5), hypercholesterolemia (6), type 2 (Table 2) (1). diabetes (6, 7), polycystic ovary syndrome (8), and renal Fasting blood glucose (FBG) and lipid profile (TG, total failure (9). PON1 is recognized as an antioxidant cholesterol, LDL-C, and HDL-C concentrations) were enzyme because it hydrolyzes lipid peroxides in oxidized measured by automated chemistry analyzer using lipoproteins. commercial available kits (Table 1). q 2011 European Society of Endocrinology DOI: 10.1530/EJE-10-0881 Online version via www.eje-online.org Downloaded from Bioscientifica.com at 09/29/2021 06:13:53AM via free access 220 M Hashemi and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2011) 164 Table 1 Biochemical parameters in metabolic syndrome (MES) (Table 3) were 69.62G59.86 and 91.64G77.45 IU/l and normal subjects. respectively. The activity of PON in MES was signi- ficantly lower than normal subjects (PZ0.01). In Normal addition, salt-stimulated PON activity was significantly Parameters MES subjects P value lower in MES (136.23G111.80 IU/l) than normal FBG (mg/dl) 118.50G58.71 85.42G12.33 !0.0001 subjects (192.24G162.68 IU/l) (PZ0.02). TG (mg/dl) 222.89G190.66 113.33G48.31 !0.0001 The serum ARE activity in MES and normal G G ! Total cholesterol 212.71 48.80 173.71 40.25 0.0001 subjects were 45.23G23.24 and 65.69G31.10 kU/l (mg/dl) HDL-C (mg/dl) 41.58G8.00 45.14G6.89 !0.0001 respectively (Table 3). LDL-C (mg/dl) 125.9G45.17 102.73G34.23 !0.0001 In males, there were no significant differences in the Height (cm) 160.71G9.70 163.46G10.17 0.02 activities of PON1 between MES (64.57G58.24 U/l) Weight (kg) 75.39G14.02 63.72G13.03 !0.0001 and normal subjects (90.01G84.17 U/l) (PZ0.106). BMI (kg/m2) 29.15G4.68 23.83G4.79 !0.0001 Waist circumference 99.32G12.41 82.39G15.77 !0.0001 While a significant difference was found regarding ARE (cm) activity in MES (64.68G35.08 kU/l) and normal SBP (mmHg) 125.89G19.78 113.81G13.75 !0.0001 subjects (40.97G16.23 kU/l) (P!0.001). DBP (mmHg) 80.84G12.25 73.85G10.63 !0.0001 In females, the activity of PON was significantly lower in the MES (72.01G60.87 U/l) than in the controls (92.82G72.49 U/l) (PZ0.039). We also found that PON activity assays were performed in the ! absence (basal activity) and presence of 1 M NaCl ARE activity was significantly lower (P 0.001) in female cases (47.25G25.75 kU/l) than in normal (salt-stimulated activity) using paraoxone (diethyl-p- G nitrophenyl phosphate) as a substrate as described subjects (62.80 27.6 kU/l). No significant correlation was observed between age previously (10). O Phenylacetate was used as a substrate to determine and PON or ARE activities (P 0.05). A significant difference was observed among MES and normal the ARE activity. The rate of phenol produced was ! continuously monitored at 270 nm at 37 8C. ARE subjects regarding the ARE activity (P 0.0001). No activity was determined using molar extinction coeffi- significant difference was observed among MES and cient of phenol (1310/M per cm) and expressed as kU/l normal subjects for TAC. In MES and normal subjects, PON activity was positively correlated with ARE activity serum (10). Z ! Z ! Serum total antioxidant capacity (TAC) was (r 0.368, P 0.0001; r 0.594, P 0.0001). While a determined by measuring their ability to reduce positive correlation was observed between PON and C C Z Z Fe3 to Fe2 , which is known as ferric reducing ability HDL-C in normal subjects (r 0.168, P 0.01), the correlation between MES and HDL-C was not significant of plasma (FRAP) assay as described previously (11). Z Z Statistical analysis was performed by commercial (r 0.122, P 0.21). Furthermore, there were no software (SPSS for Windows, V17) using independent correlations between MES and normal subjects regard- ing PON and cholesterol, LDL-C, triglyceride, TAC, and sample t-test and the Pearson correlation coefficient test. O A P value !0.05 was considered statistically significant. body mass index (BMI) (P 0.05). Results Discussion The study consisted of 106 MES (34 males and 72 In this study, we found that PON and ARE activities females; age 43.54G14.07) and 231 normal subjects were significantly lower in MES when compared with (97 males and 134 females; age 35.64G13.27). The normal subjects. The formation of free radicals is a levels of PON1 activity in MES and healthy subjects normal outcome of a variety of essential biochemical reactions and can occur at elevated rates under Table 2 Criteria for diagnosis of the metabolic syndrome according pathophysiological circumstances (12, 13). The phys- to the national cholesterol education program (NCEP) ATP III. iological role of antioxidants is to prevent damage to Criterion NCEP ATP IIIa Table 3 The levels of paraoxonase (PON), salt-stimulated PON, arylesterase activities, and total antioxidant capacity (TAC) in Waist (cm) metabolic syndrome (MES) and healthy subjects. Male R102 R Female 88 Normal HDL (mg/dl) MES subjects P value Male !40 Female !50 PON1 activity (IU/l) 69.62G59.86 91.64G77.45 0.01 Triglyceride (mg/dl) R150 Salt-stimulated 136.23G111.80 192.24G162.68 0.02 Fasting glucose (mg/dl) R100 PON (IU/l) Blood pressure (mmHg) R130/85 ARE (kU/l) 45.23G23.24 65.69G31.10 !0.0001 TAC (mmol/l) 972.46G374.13 966.97G380.60 0.912 aThree of five required. www.eje-online.org Downloaded from Bioscientifica.com at 09/29/2021 06:13:53AM via free access EUROPEAN JOURNAL OF ENDOCRINOLOGY (2011) 164 Serum paraoxonase activity in MES 221 cellular components arising as a consequence of Evaluation, And Treatment of High Blood Cholesterol In Adults chemical reactions involving free radicals. PON1 is a (Adult Treatment Panel III). Journal of the American Medical Asso- ciation 2001 285 2486–2497. (doi:10.1001/jama.285.19.2486) specific antioxidative enzyme with both PON and ARE 2 Mackness MI, Arrol S & Durrington PN. Paraoxonase prevents activities. There is little information regarding the levels accumulation of lipoperoxides in low-density lipoprotein. FEBS Letters of PON and ARE in MES.