The paraoxonases: role in human diseases and methodological difficulties in measurement.

Research into the paraoxonase (PON) gene family has flourished over the past few years. In the 1970s and 1980s, only PON1 was known, and the investigations were conducted, essentially, by toxicologists focusing on protection against organophosphate poisoning. Since then, two new members of the family, PON2 and PON3, have been identified, both being shown to play antioxidant and anti-inflammatory roles.

Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease.

Background: Paraoxonase-1 (PON1) is an antioxidant enzyme synthesized by the liver. It protects against liver impairment and attenuates the production of the pro-inflammatory monocyte chemoattractant protein-1 (MCP-1). We investigated the relationships between hepatic PON1 and MCP-1 expression in rats with liver disease and explored the possible molecular mechanisms involved.

Increased susceptibility to exacerbated liver injury in hypercholesterolemic ApoE-deficient mice: potential involvement of oxysterols.

The contribution of metabolic factors to the severity of liver disease is not completely understood. In this study, apolipoprotein E-deficient (ApoE-/-) mice were evaluated to define potential effects of hypercholesterolemia on the severity of carbon tetrachloride (CCl4)-induced liver injury. Under baseline conditions, hypercholesterolemic ApoE-/- mice showed increased hepatic oxidative stress (SOD activity/4-hydroxy-2-nonenal immunostaining) and higher hepatic TGF-beta1, MCP-1, and TIMP-1 expression than wild-type control mice.

The measurement of the lactonase activity of paraoxonase-1 in the clinical evaluation of patients with chronic liver impairment.

Aims: We investigated the analytical performance of a new assay of the lactonase activity of paraoxonase-1 and its efficacy in the assessment of liver damage.

Design And Methods: Serum lactonase activity was determined by the hydrolysis of 5-thiobutyl butyrolactone in 633 healthy individuals and 369 patients with chronic liver disease. Paraoxonase-1, 2, and 3 gene polymorphisms were analyzed by the MassArray method.

Selective extraction, separation, and identification of anthocyanins from Hibiscus sabdariffa L. using solid phase extraction-capillary electrophoresis-mass spectrometry (time-of-flight /ion trap).

A method for selective extraction using SPE, electrophoretic separation at basic condition and the identification by using exact masses and fragmentation patterns has been developed in order to know the anthocyanins in dried calyces of Hibiscus sabdariffa L. A detailed and comparative study of several extraction procedures has been carried out to obtain the maximum number of anthocyanidins from the calyces and then a CE-TOF-MS method in positive mode using ESI has been developed for the separation and rapid identification of anthocyanins in H. sabdariffa L.

Immunohistochemical analysis of paraoxonases-1, 2, and 3 expression in normal mouse tissues.

The paraoxonase (PON) enzyme family, comprising PON1, PON2, and PON3, are antioxidant enzymes that degrade oxidised phospholipids. We describe the immunohistochemical localisation of the PON proteins in the normal mouse. Antibodies were obtained by inoculating rabbits with peptides derived from specific sequences of mature PONs.

Serum paraoxonase undergoes inhibition and proteolysis during experimental acute pancreatitis.

Oxidative stress has a primary role in the pathogenesis of severe acute pancreatitis. Then, the antioxidant capacity is a critical factor in the progression of this disease. Serum paraoxonase-1 (PON1) is an esterase associated with high-density lipoprotein, which clinical interest resides in its ability to prevent or limit the lipid oxidation.

Moderately high folic acid supplementation exacerbates experimentally induced liver fibrosis in rats.

Under certain clinical circumstances, folic acid can have undesirable effects. We investigated the following: (i) the effects of moderately high folic acid supplementation on the course of liver impairment in CCl(4)-treated rats and (ii) the influence of folic acid supplements on the hepatic recovery following the interruption of the CCl(4)-induced toxic injury. Four experimental groups of rats were used: CCl(4)-treated rats (0.

Changes in the expression of genes related to apoptosis and fibrosis pathways in CCl4-treated rats.

Chronic liver diseases are accompanied by changes in the biochemical pathways related to the regulation of apoptosis and extra-cellular matrix deposition. The present study was designed to investigate, using low density arrays, changes in the hepatic gene expression together with hepatic biochemical and histological alterations in rats that had liver impairment induced by chronic exposure to CCl(4). Further, we examined the possible recovery of genetic and pathological changes following the cessation of the hepatotoxic injury.

Deficiency in monocyte chemoattractant protein-1 modifies lipid and glucose metabolism.

We describe the effect of MCP-1 deficiency in mice rendered hyperlipemic by the concomitant ablation of the LDL receptor. The MCP-1(-/-)LDLr(-/-) mice in comparison with LDLr(-/-) mice showed a decreased lipoprotein clearance, derangements in free fatty acids delivery and less glucose tolerance when fed a regular chow, and they showed a partial resistance to alterations in glucose and lipid metabolism induced by dietary fat and cholesterol. They also were less prone to the development of diet-induced obesity.

The role of immunity and inflammation in the progression of atherosclerosis in patients with HIV infection.

Background And Purpose: The initial steps of atherosclerosis and the entry of HIV into the cell share similar biological mechanisms. Therefore, our hypothesis is that the progression of atherosclerosis in patients with HIV infection can be influenced by variations in genes implicated in both processes.

Methods: The progression of atherosclerosis over a 2-year follow-up period was measured as the combined carotid and femoral intima media thickness (IMT) in 141 patients with HIV infection.

The results in rodent models of atherosclerosis are not interchangeable: the influence of diet and strain.

The determinant factors for the development of atherosclerosis in response to dietary cholesterol were examined in two animal models to assess the comparability of results. We studied 128 male Apo E(-/-) and 128LDLr(-/-) mice randomly assigned to baseline (n=8) and 5 groups (n=24 each) that differed only in their dietary fat and cholesterol supplements. At 10, 16, 24 and 32 weeks of age, 8 animals from each group were sequentially sacrificed and the variables analyzed.

Monocyte chemoattractant protein-1 and atherosclerosis: is there room for an additional biomarker?

Atherosclerosis is an inflammatory disease in which several chemokines are implicated. The roles of these molecules extend from the recruitment of circulating inflammatory cells to the activation of inflammatory and pro-thrombotic cascades, which ultimately leads to an atherosclerosis-related event. One of the most studied chemokines is monocyte chemoattractant protein-1 (CCL2), which has been strongly linked to atherosclerosis in both animal and human studies.

Serum paraoxonase-1 in chronic alcoholics: relationship with liver disease.

Objectives: To investigate the relationship between serum paraoxonase-1 and liver damage in chronic alcoholic patients. To assess the diagnostic accuracy of paraoxonase-1 plus standard biochemical tests in the assessment of liver damage in alcoholics.

Design And Methods: We studied 328 chronic alcoholics and 368 healthy individuals.

Administration of exogenous erythropoietin beta affects lipid peroxidation and serum paraoxonase-1 activity and concentration in predialysis patients with chronic renal disease and anaemia.

1. Patients with advanced chronic renal disease and anaemia have decreased serum paraoxonase-1 (PON1) activity and an increased degree of oxidative stress compared with normal subjects. The present study investigated the effects of treatment of anaemia with exogenous recombinant erythropoietin (EPO) beta and iron on levels of antibodies against oxidized low-density lipoproteins (ox-LDL), as well as on serum PON1 activity and concentration, in predialysis patients with chronic renal disease.

Rosiglitazone modulates fasting and post-prandial paraoxonase 1 activity in type 2 diabetic patients.

1. In the present study, we have explored the effect of rosiglitazone on post-prandial paraoxonase (PON)-1, an enzyme with potent anti-oxidant properties that may protect against atherosclerosis because increased post-prandial lipaemia, although sometimes understated, is part of the diabetic dyslipidaemia. 2.

Serum paraoxonase-1 activity and concentration are influenced by human immunodeficiency virus infection.

Background: Higher high-density lipoprotein concentrations are associated with a better disease course in HIV-infected patients. Paraoxonase-1, an enzyme contained within high-density lipoproteins, is thought to hydrolyse oxidised lipids. The aim of the present study was to investigate the relationships between HIV infection and the circulating activity and concentration of paraoxonase-1, and the concentration of high-density lipoproteins, apolipoprotein A-I and oxidised low-density lipoproteins.

Influence of a monocyte chemoattractant protein 1 mutated allele on the response to protease inhibitor-based antiretroviral therapy.

Background: Antiretroviral drug efficacy has been widely studied in relation to viral factors. Mutations in the HIV co-receptors and their natural chemokines, however, may be critical in HIV infection and treatment response. We compared the efficacy of protease inhibitor (PI) treatment among PI-naïve patients grouped according to whether they carried the chemokine CC motif receptor 2 (CCR-2) 64I and monocyte chemoattractant protein 1 (MCP-1)-2518G alleles.

Effects of rosiglitazone and metformin on postprandial paraoxonase-1 and monocyte chemoattractant protein-1 in human immunodeficiency virus-infected patients with lipodystrophy.

Highly active antiretroviral therapy in Human Immunodeficiency Virus (HIV) has been associated with lipodystrophy, insulin resistance and atherosclerosis. We investigated the effects of rosiglitazone or metformin on fasting and postprandial inflammatory and antioxidant variables in HIV-infected males with lipodystrophy. Thirty-one patients were randomly assigned to receive either rosiglitazone (4 mg twice daily) or metformin (1 g twice daily) for 26 weeks.

Manipulation of inflammation modulates hyperlipidemia in apolipoprotein E-deficient mice: a possible role for interleukin-6.

There are increasing evidences showing that inflammation participates in atherosclerosis. Therefore, the therapeutic use of anti-inflammatory agents should be considered. We have induced chronic, aseptic inflammation upon the injection of turpentine and tested the effect of dexamethasone on lipoprotein metabolism and, consequently, atherosclerosis in apolipoprotein E-deficient mice.

Longitudinal changes in serum paraoxonase-1 activity throughout normal pregnancy.

The aim of this study was to investigate the longitudinal changes in serum paraoxonase-1 (PON1) activity from preconception throughout normal pregnancy and their relationships with maternal dietary vitamin C and E intake. The study was performed in 35 women (studied at preconception, at 8, 20 and 32 weeks of pregnancy, and at labour). PON1 activity decreased significantly from 145.

HIV-infected patients with lipodystrophy have higher rates of carotid atherosclerosis: the role of monocyte chemoattractant protein-1.

Individuals with HIV-1 infection are at increased risk for cardiovascular events, and lipodystrophy is generally associated with pro-atherogenic metabolic disturbances. We conducted a case-control study to assess the presence of sub-clinical atherosclerosis in HIV-1-infected patients with or without lipodystrophy (LD) and to evaluate the influence of monocyte chemoattractant protein-1 (MCP-1) on the development of both carotid atherosclerosis and LD. The study population consisted of 43 patients with LD and 86 patients without LD.