PON1 arylesterase activity, HDL functionality and their correlation in malnourished children.

Background The study was done to assess high-density lipoprotein (HDL) functionality and to correlate this with paraoxonase 1 (PON1) activity in malnourished children. It aimed to find the effect of malnutrition on changes in PON1 activity, HDL functionality, lipid profile and lipid hydroperoxide formation. Methods This case control study included 30 malnourished children (up to age 5 years) and 30 healthy controls in the paediatric inpatient department of SRTR Government Medical College Ambajogai, India. Clinically diagnosed cases depending on anthropometric indices were selected. Serum PON1 activity by using phenyl acetate as a substrate, HDL functionality by haemin by its protection on H2O2 and haemin induced LDL oxidation, lipid profile by routine enzymatic methods and lipid hydroperoxide using the FOX2 assay were measured. Results Malnourished children had significantly decreased PON1 activity (106.6 ± 12.74** vs. 132.23 ± 28.49 IU/L), HDL functionality (116.55 ± 8** vs. 132.29 ± 10.9%), total cholesterol (TC) (102.5 ± 16** vs. 116.4 ± 12.65 mg/dL), HDL-cholesterol (C) (33.41 ± 9.74** vs. 40.55 ± 5.85 mg/dL) and reduced total protein level (5.56 ± 0.91* vs. 6.06 ± 1.055) higher triglycerides (TG) (146.76 ± 34.97* vs. 125.96 ± 17.21 mg/dL) level and total hydroperoxide (TPX) levels (5.568 ± 1.70** vs. 3.22 ± 1.52 µM/L). *p < 0.05 **p < 0.001. PON1 activity (r2 = 0.576) and TC (r2 = 0.567) shows significant positive correlation with HDL functionality. PON1 activity, HDL-C, HDL functionality and TPX shows independent contribution towards malnutrition in children in multivariate and univariate logistic regression. TC lost its significance in multivariate regression. Conclusions Malnutrition leads to decrease in HDL functionality and increase in hydroperoxide levels with a decrease in PON1 activity.

Paraoxonase activity in metabolic syndrome in children and adolescents.

BACKGROUND: Metabolic syndrome (MetS) is a collection of various interrelated risk factors that appear to have an impact as development of atherosclerotic cardiovascular disease (CVDs). Epidemic of childhood and adolescent's obesity has increased interest in the metabolic syndrome (MS) due to the potential projection into adulthood. The prevalence of MS in adolescents has been estimated to be 6.7% in young adults and 4.2% in adolescents. We aimed to study the MetS in children and adolescents with respect to metabolic changes. METHODS: The international Diabetes Federation criteria were used for the selection of cases. Serum paraoxonase 1 (PON1) activities were measured using spectrophotometer. Statistical analysis was done using MyStat statistical software. RESULTS: Serum PON1 arylesterase (ARE) and lactonase (LACT) activities were found to be reduced significantly in patients with MetS than in controls. Regression analysis showed a significant correlation between PON1 activities and body mass index. Area under curve (AUC) found to increase from HDL to PON1 ARE to PON1 LACT. CONCLUSIONS: From the present study, it is clear that in children and adolescents, reduction in PON1 activities in MetS is mainly due either to abnormalities with synthesis or secretion of HDL cholesterol or oxidative stress as a consequence of excess production of the free radicals. This study also iterates that it is the quality and not the quantity of HDL cholesterol which is important while studying the pathophysiology of MetS.

The Paraoxonase 1 Arylesterase Activity, Total Oxidative Stress, Nitric Oxide and Vitamin C Levels in Maternal Serum, and Their Relation to Birth Weight of Newborn.

AIM: Aim of this study is to find out clinical relevance of estimating PON1 arylesterase activity, total oxidative stress (TOS), nitric oxide (NO), and vitamin C levels in maternal serum for prediction of birth weight of newborn. METHODS: We have investigated the PON1 arylesterase activity, TOS, NO, vitamin C, total protein, and albumin levels in 56 postnatal clinic patients having newborn weighing <2500 gm (low birth weight) and compared with 56 postnatal clinic patients having newborn weighing >2500 gm. Samples were collected immediately after delivery. RESULTS: PON1 arylesterase activity levels show significant decrease in cases as compared to controls (93.27 ± 13.76 kU/l vs. 112.77 ± 9.42 kU/l). Nitric oxide (nitrate + nitrite) levels are also found to be significantly decreased in cases with respect to controls (22.89 ± 2.65 umol/l vs. 24.73 ± 3.80 umol/l). Total oxidative stress is significantly increased in cases than in control subjects (23.34 ± 2.64 µmol H2O2 equiv./l vs. ± 21.43 ± 2.47 µmol H2O2 equiv/l). Vitamin C levels are also significantly decreased in cases as compared to controls (1.23 ± 0.25 mg/dl vs. 1.34 ± 0.28 mg/dl). Positive correlation between neonatal birth weight and maternal serum PON1 arylesterase activity (r = 0.682, p < 0.05) while negative correlation is obtained between neonatal birth weight and maternal serum oxidative stress (r = -0.478, p < 0.05). Logistic regression analysis is applied for assessing predictive utility which demonstrated a significant association of birth weight with PON1 arylesterase activity (AUC = 0.960, Naglekerke's R (2) = 0.793, p < 0.05). CONCLUSION: Decreased arylesterase activity and antioxidant vitamin C levels with increased total oxidative stress in maternal serum may be considered as the additional risk factors for the development of low birth weight newborn.

Small Dense Low Density Lipoprotein Cholesterol, Paraoxonase 1 and Lipid Profile in Postmenopausal Women: Quality or Quantity?

BACKGROUND AND AIMS: Atherosclerosis, the root cause of cardiovascular disease (CVD), has a number of risk factors-some modifiable and some not. CVD increases in women particularly during the postmenopausal period. Small dense low-density lipoprotein (sdLDL), a subclass of LDL, is an important determinant of atherosclerosis in postmenopausal women. Paraoxonase1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme that prevents oxidative modifications in LDL and HDL. With this background, we studied the sdLDL-C, PON1 and lipid profile in postmenopausal women to compare between quality and quantity of LDL. METHODS: We studied 80 pre- and postmenopausal women (40/group). The following parameters were studied: lipid profile, sdLDL-C and PON1 levels. With proper statistical tools the correlation between these parameters was studied. RESULTS: Postmenopausal women, in comparison with premenopausal women, have significantly increased levels of serum triglycerides and sdLDL-C and very-low-density lipoprotein cholesterol (VLDL-C) and significantly decreased levels of HDL-C and PON1. PON1 activity was negatively correlated with age, TC, TG, LDL-C and sdLDL-C (r = -0.574, -0.119, -0.226, -0.473 and -0.455, respectively) and positively correlated with HDL-C (r = 0.368), whereas sdLDL-C was positively correlated with age, TC, TG, LDL-C (r = 0.633, 0.485, 0.561 and 0.705, respectively) and negatively with HDL-C (r = -0.235). Stepwise multiple regression analysis demonstrated HDL-C and menopausal status as the best determinant for PON1 (R(2) = 0.320, p < 0.05) and menopausal status, LDL-C, TG, and TC were the best determinants for sdLDL-C (R(2) = 0.606, p < 0.05). CONCLUSION: The results of the present study suggest quality, i.e., sdLDL-C, is more important than only LDL-C levels. Similarly, decrease in PON1 and increase in sdLDL-C go hand in hand. This shows that antioxidant capacity is compromised with a qualitative downfall in lipoproteins in postmenopausal women.

Paraoxonase1, its Q192R polymorphism and HDL-cholesterol in relation to intensive cardiac care unit stay in ischemic heart disease.

AIMS AND OBJECTIVES: The present study was evaluated the atheroprotective potential of paraoxonase1 (PON1) and its Q192R polymorphism, to determine whether this polymorphism, which is responsible for differential PON1 activity plays any role in the pathogenesis, severity and extent of coronary artery disease (CAD). MATERIALS AND METHODS: This hospital-based cross-sectional study investigated 60 diagnosed cases of CAD and 60 age and gender matched controls. All were assessed for serum PON1 activity, PON1 Q192R polymorphism and for classical cardiovascular risk factors. Individual serum phenotyping for PON1 Q192R polymorphism was determined by double substrate hydrolysis assay. Severity of CAD was assessed by the length of intensive cardiac care unit (ICCU) stay. RESULTS: Serum PON1 activity is significantly reduced in cases of CAD (92.6 ± 31.13 IU/L when compared with controls (105.26 ± 32.53 IU/L). Furthermore, serum arylesterase activity is reduced in CAD patients (90.31 ± 23.26 kU) when compared with the control subjects (101.61 ± 28.68 kU). Serum PON1 and arylesterase activities are significantly negatively correlated with the length of ICCU stay (r = -393 and r = -374 respectively). There is no significant difference in the occurrence of CAD and length of ICCU stay among the PON1 phenotypes (P = 0.92). Logistic regression analysis after adjustment of established risk factors revealed no significant association between CAD risk and PON1 Q192R polymorphism (odds ratios: 1.179 [95% confidence intervals: 0.507-2.744], P = 0.702). SUMMARY AND CONCLUSIONS: The current study demonstrates that the activity of the PON1 enzyme may be more important factor than the PON1 Q192R polymorphism in the severity and extent of CAD.

Correlation of paraoxonase1 activities with birth weight.

OBJECTIVES: To evaluate arylesterase and lactonase activity of paraoxonase (PON)1 in cord blood of neonates in relation to their birth weight. The authors hypothesized that cord blood PON1 arylesterase and lactonase activities will be compromised in neonates having low birth weight. METHODS: Eighty neonates born in authors' hospital, irrespective of mode of delivery were included. Forty children with low birth weight were included in case group and 40 with normal birth weight were included as controls. PON1 arylesterase and lactonase activities were measured. RESULTS: Serum arylesterase activity decreased significantly in low birth weight babies (p < 0.05). Linear regression analysis (R = 0.728) indicated significant correlation between arylesterase and birth weight. Serum lactonase activity was also reduced in low birth weight babies. Its linear regression analysis (R = 0.727) indicated significant correlation between lactonase and birth weight. CONCLUSIONS: PON 1 activity is significantly reduced among low birth weight babies in comparison to normal weight babies.

Serum lactonase and arylesterase activities in alcoholic hepatitis and hepatitis B.

BACKGROUND: PON1 is an HDL-associated enzyme having antioxidant activity. PON1 is synthesized in the liver, and there is decreased synthesis of PON1 with increased lipid peroxidation. The study was carried with the aim of establishing whether chronic liver disease (CLD) produced any significant changes in serum arylesterase (AE) and lactonase activities of PON. The second objective was to determine whether there was any correlation between serum AE and lactonase activities and the various routine liver function tests. The usefulness of adding serum lactonase and AE activity to standard liver function tests was analyzed by multiple logistic regression analysis. Finally, the diagnostic efficacy or analytical performance of AE and lactonase in assessing patients with CLD was determined using 'receiver operating characteristic' (ROC) plot. METHODS: The study group consisted of 120 subjects; 60 were patients with liver disease out of which 40 were having chronic alcoholic liver disease and 20, acute viral hepatitis B, and 60 were healthy controls. Serum PON1 lactonase activity was measured manually using dihydrocoumarin, and AE activity was measured using phenylacetate as substrate. Liver function tests (bilirubin, albumin, AST, ALT, alkaline phosphatise) were done by standard technique. RESULT: The serum lactonase and AE activities were decreased significantly in patients with chronic alcoholic liver disease (p < 0.001, p < 0.001) and acute viral hepatitis B (p < 0.001, p < 0.001). Both measurements showed higher efficiency in testing liver dysfunction in multivariate regression analysis. Model 1 consisted of bilirubin, albumin, AST, ALT, and alkaline phosphatase, R2 = 0.912. Model 2 consisted of model 1+arylesterase having higher R2 = 0.0.954, and model 3 consisted of model 1+lactonase having R2 = 0.962. ROC plots demonstrated a high diagnostic accuracy for serum PON1 lactonase (area under ROC curve = 0.982) and serum PON1 arylesterase (area under ROC curve = 0.986). CONCLUSION: Low PON1 lactonase and AE activity were found in acute viral hepatitis B and in chronic alcoholic hepatitis.