Paraoxonase 1 serum activity in women: the effects of menopause, the C(-107)T polymorphism and food intake

ABSTRACT Objective The aims of this study were to investigate changes in serum paraoxonase 1 (PON1) activity in women at the pre and postmenopausal stages and its association with the PON1 C(-107)T polymorphism and food intake profile. Subjects and methods A cross-sectional study with female patients aged between 35 and 59 years old was conducted. Women were divided into two groups: premenopausal (n = 40) and postmenopausal (n = 36). Women enrolled in the study had serum PON1, total cholesterol, HDL, LDL, glucose and HbA1c, as well as the BMI measured. Additionally, women were genotyped for the PON1 T(-107)C polymorphism and the food intake profile was obtained through interview. Results Glucose (p = 0.03), HbA1c (p = 0.002) and total cholesterol (p = 0.002)concentrations were higher in post than premenopausal women, however PON1 activity was not different (p > 0.05). Carriers of the C allele had higher PON1 activity (CC: 88.9 ± 6.5 U/mL and CT: 79.9 ± 4.7 U/mL) than women of the TT genotype (66.6 ± 5.9 U/mL) (p < 0.05). However, the model predicting PON1 activity was slightly better when genotype, total fat and cholesterol content in the diet were all included. Conclusion In sum, we observed that the PON1 C(-107)T genotype was the major regulator of PON1 activity, and menopause had no effect on PON1 activity. The lipid and glycemic profile were altered in postmenopausal women.

Investigation of the antioxidant effects of pheniramine maleate and nebivolol on testicular damage in rats with experimentally induced testis torsion

Abstract Purpose: To investigate the biochemical, histopathologic, and spermatogenetic changes in the detorsionated testicle after experimental torsion and to study the antioxidant effects of pheniramine maleate and nebivolol. Methods: Twenty-four Sprague-Dawley male rats were divided into 4 groups: Group 1: Sham; Group 2: Torsion/Detorsion (T/D); Group 3: T/D + Pheniramine maleate (PM); Group 4: T/D + Nebivolol (NB) group. Paroxanase (PON), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stres index (OSI) were measured, and spermatogenetic and histopathologic evaluation was performed in tissue and blood samples. Results: The evaluation of tissue TAS indicated no statistically significant difference in Group 3 compared to Group 2. A statistically significant increase was detected in Group 4 compared to Group 2. Serum PON levels revealed a statistically significant increase in Groups 3 and 4 compared to Groups 1 and 2. The Johnsen testicular biopsy score decreased in Groups 3 and 4, but the decrease was not statistically significant. Conclusions: Pheniramine maleate and nebivolol have antioxidant effects against ischemia-reperfusion damage. They also support tissue recovery, which is more significantly observed by nebivolol.

Serum paraoxonase, arylesterase, and glutathione-s-transferase activities and oxidative stress levels in patients with mushroom poisoning

OBJECTIVES: Consumption of toxic species of mushrooms may have detrimental effects and increase oxidative stress. Paraoxonase, arylesterase and glutathione-S-transferase are antioxidants that resist oxidative stress. In this study, we analyzed the changes in these enzymes during intoxication due to mushrooms. METHODS: The study enrolled 49 adult patients with a diagnosis of mushroom poisoning according to clinical findings and 49 healthy volunteers as the control group. The patients with mild clinical findings were hospitalized due to the possibility that the patient had also eaten the mushrooms and due to clinical findings in the late period, which could be fatal. Paraoxonase, arylesterase, and glutathione-S-transferase concentrations, as well as total antioxidant and oxidant status, were determined in the 49 patients and 49 healthy volunteers by taking blood samples in the emergency department. RESULTS: While paraoxonase, arylesterase, and total antioxidant status were significantly decreased in the patient group (p<0.05), glutathione-S-transferase, total oxidant status and the oxidative stress index were significantly higher (p<0.05). There was a positive correlation between the hospitalization time and the oxidative stress index (r=0.752, p<0.001), whereas a negative correlation was found with glutathione-S-transferase (r=-0.420, p=0.003). CONCLUSION: We observed a significant decrease in paraoxonase and arylesterase and an increase in glutathione-S-transferase and oxidative stress indexes in patients with mushroom poisoning, indicating that these patients had an oxidative status. In particular, a low total antioxidant status and high oxidative stress index may gain importance in terms of the assessment of hospitalization duration.

Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score

ABSTRACT Objective Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. Materials and methods Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. Results Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. Conclusion Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.

The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia / O efeito do extrato de semente de uva vermelha na atividade do soro paraoxonase em doentes com hiperlipidemia leve a moderada

ABSTRACT: CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

RESUMO: CONTEXTO E OBJETIVO: Extrato de semente de uva vermelha (RGSE) contém complexos de proantocianidinas oligoméricas como classe de flavonoides. Estes compostos são antioxidantes potentes e exercem muitos efeitos de promoção da saúde. Este estudo visou determinar os efeitos de RGSE nos níveis séricos de triglicérides (TG), colesterol total (TC), colesterol de lipoproteína alta-densidade (HDL-C), colesterol de lipoproteína baixa-densidade (LDL-C), apolipoproteína AI (apo-AI) e atividade de paraoxonase (PON) em pacientes com hiperlipidemia leve a moderada (MMH). DESENHO E LOCAL: Estudo clínico randomizado duplo-cego controlado com placebo, realizado no Hospital Shahid-Modarres (Teerã, Irã) e na Universidade de Ciências Médicas de Tabriz. Setenta pacientes com MMH foram aleatoriamente designados para receber tratamento (200 mg/dia de RGSE) ou placebo durante oito semanas. RESULTADOS: Elevação significativa nos níveis séricos de apo-AI (P = 0,001), HDL-C (P = 0,001) e atividade de PON (P = 0,001) e diminuição marcada nas concentrações de TC (P = 0,015), TG (P = 0,011) e LDL-C (P = 0,014) foram encontradas nos casos. Atividade de PON mostrou correlação significativa com apo-AI (r = 0,270; P < 0,01) e HDL-C (r = 0,45; P < 0,001). Diferenças significativas entre os grupos RGSE e controle (antes e após tratamento) para TC (P = 0,001), TG (P = 0,001), PON (P = 0,03), apo-AI (P = 0,001) e LDL-C (P = 0,002) foram observadas. CONCLUSÃO: É possível que RGSE aumente atividade de PON principalmente através da elevação dos níveis de HDL-C e apo-AI em pacientes MMH. Ele pode, assim, ter efeitos benéficos potenciais na prevenção de estresse oxidativo e aterosclerose nesses pacientes.

p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample / O SNP p.Q192R da PON1 não Parece Associar-se a Fatores de Risco para a Aterosclerose Carotídea em Amostra de População Brasileira Normolipidêmica e Assintomática

Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL).

Effectiveness of Limberg and Karydakis flap in recurrent pilonidal sinus disease

OBJECTIVE: Sacrococcygeal pilonidal sinus is common in young men and may recur over time after surgery. We investigated whether a factor exists that can aid in the determination of the preferred technique between the early Limberg flap and Karydakis flap techniques for treating recurrent pilonidal sinus. MATERIALS AND METHODS: This prospective and randomized study enrolled 71 patients with recurrent pilonidal sinus in whom the Limberg flap or Karydakis flap techniques were applied for reconstruction after excision. Patients were divided into two groups as follows: 37 patients were treated with the Limberg flap technique and 34 patients were treated with the Karydakis flap technique. Fluid collection, wound infection, flap edema, hematoma, partial wound separation, return to daily activities, pain score, complete healing time, painless seating and patient satisfaction were compared between the groups. ClinicalTrial.gov: NCT02287935. RESULTS: The development rates of total fluid collection, wound infection, flap edema, hematoma, and partial wound separation were 9.8%, 16%, 7%, 15% and 4.2%, respectively; total flap necrosis was not observed in any patient (p<0.001). During the average follow-up of 28 months, no patients (0%) developed recurrent disease. The two groups differed with respect to early surgical complications (p<0.001). CONCLUSION: In this study, use of the Limberg flap was associated with lower complication rates, shorter length of hospital stay, early return to work, low pain score, high patient satisfaction and better complete healing duration. Therefore, we recommend the Limberg flap for treatment of recurrent pilonidal sinus. .

Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study / Estado oxidante-antioxidante em crianças egípcias com anemia falciforme: estudo baseado em um único centro

OBJECTIVE: the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia. METHODS: the serum levels of total antioxidant capacity (TAO), paraoxonase (PON), vitamin E, nitrite, and malondialdehyde (MDA) were measured in 40 steady state children with homozygous sickle cell anemia (24 males and 16 females) and 20 apparently healthy age- and gender-matched controls. RESULTS: mean serum TAO, PON, vitamin E, and nitrite levels were significantly lower in the group with sickle cell anemia, whereas mean serum MDA was significantly higher in these children compared to controls. No significant differences in mean levels of TAO, PON, nitrite, vitamin E, and MDA were found in sickle cell anemia patients receiving hydroxyurea when compared with those not receiving hydroxyurea. A significant negative correlation between serum nitrite and the occurrence of vaso-occlusive crises (VOC) was observed (r = -0.3, p = 0.04). PON level was found to be positively correlated with patients' weight and BMI (r = -0.4, p = 0.01; r = -0.7, p < 0.001, respectively), but not with frequency of VOC. The area under the curve of serum nitrite in predicting occurrence of VOC was 0.782, versus 0.701 for PON, and 0.650 for TAO (p = 0.006). Serum MDA was not correlated with nitrite, PON, TAO, or vitamin E levels. No significant correlations were detected between serum nitrite and hemoglobin or antioxidant enzymes. CONCLUSION: children with sickle cell anemia have chronic oxidative stress that may result in increased VOC, and decreased serum nitrite may be associated with increases in VOC frequency. A novel finding in this study is the decrease in PON level in these patients, which is an interesting subject for further research. .

OBJETIVO: o presente estudo foi realizado com o objetivo de investigar o estado oxidante-antioxidante em crianc¸as egípcias com anemia falciforme. MÉTODOS: dosamos os níveis séricos da capacidade antioxidante total (CAT), paraoxonase (PON), vitamina E, nitrito e malondialdeído (MDA) em 40 crianças estáveis com anemia falciforme homozigótica (24 meninos e 16 meninas), e 20 controles pareados por idade/sexo aparente-mente saudáveis. RESULTADOS: os níveis séricos médios da CAT, PON, vitamina E e nitrito foram significativamente menores, ao passo que o nível sérico médio de MDA foi significativamente maior em crianças com anemia falciforme (AF), em comparação aos controles. Não foram encontradasdiferenças significativas nos níveis médios de CAT, PON, nitrito, vitamina E e MDA em pacientescom AF em tratamento com hidroxiureia, em comparação aos que receberam hidroxiureia. Encontramos uma correlação negativa significativa entre o nitrito sérico e a ocorrência decrises vaso-oclusivas agudas (CVO) (r = -0,3, p = 0,04). Descobrimos que o nível de PON está correlacionado positivamente com o peso e o IMC dos pacientes (r = -0,4; p = 0,01; r = -0,7; p < 0,001, respectivamente), porém não com a frequência de CVO. A área sob a curva (ASC) donitrito sérico na previsão da ocorrência de CVO foi 0,782, em comparação a 0,701 para PON e 0,650 para CAT (p = 0,006). O MDA não está correlacionado a nitrito, PON, CAT ou vitamina E. Não foram detectadas correlações significativas entre nitrito sérico e hemoglobina ou enzimas antioxidantes. CONCLUSÃO: crianças com AF apresentam estresse oxidativo crônico que pode resultar emaumento das CVO. Em crianças com AF, a redução nos níveis de ...

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Paraoxonase 1 status in keratoconus: a preliminary study of activity and polymorphism / Estatus de la paraoxonasa 1 en el queratocono: estudio preliminar de actividad y polimorfismo

OBJECTIVE: To determine the activity of paraoxonase 1 (PON1) in keratoconus in a Malaysian population in comparison with non-keratoconic subjects. METHODS: Clinical eye examinations were performed on patients with keratoconus and non-keratoconic subjects after questionnaires were completed. Blood samples were collected and subjected to spectrophotometry analysis of paraoxonase and diazoxonase activities for the determination of the status of PON1 of every individual. RESULTS: Of the 11 keratoconic patients and 55 non-keratoconic control samples collected, eight patients of Indian ethnicity were keratoconic (73%), whereas 33 non-Indians were non-keratoconic (60%; p = 0.047). Paraoxonase activity was lower in Indians compared to the non-Indians ie Malays and Chinese (p = 0.008). Keratoconic subjects had a lower paraoxonase activity compared to non-keratoconics (p = 0.038). CONCLUSIONS: The reduced paraoxonase activity in keratoconic patients suggests that the keratoconic corneas were more susceptible to oxidative stress. Reduced paraoxonase activity and keratoconus status appears to be associated with ethnicity.

OBJETIVO: Determinar la actividad de paraoxonasa 1 (Pon 1) en el queratocono en una población malaya, en comparación con sujetos no queratocónicos. MÉTODOS: Se realizaron exámenes clínicos oculares a pacientes con queratocono y a sujetos no queratocónicos luego que los mismos respondieran a los cuestionarios. Se recogieron muestras de sangre, que fueron entonces sometidas a análisis espectrofotométrico en relación con las actividades de la paraoxonasa y la diazoxonasa para la determinación del estatus de la paraoxonasa 1 de cada individuo. RESULTADOS: De los 11 pacientes queratocónicos y las 55 muestras de control no queratocónicas recogidas, 8 pacientes de etnicidad india fueron queratocónicos (73%), mientras que 33 no indios fueron no queratocónicos (60%; p = 0.047). La actividad de la paraoxonasa fue más baja en los indios en comparación con los no indios, es decir, los malayos y los chinos (p = 0.008). Los sujetos queratocónicos tenían una actividad de la paraoxonasa más baja, comparada con los no queratocónicos (p = 0.038). CONCLUSIONES: La actividad de la paraoxonasa reducida en los pacientes queratocónicos sugiere que las córneas queratocónicas son más susceptibles al estrés oxidativo. La actividad de la paraoxonasa reducida y el estatus del queratocono parecen estar asociados con la etnicidad.

Simultaneous transfer of cholesterol, triglycerides, and phospholipids to high-density lipoprotein in aging subjects with or without coronary artery disease

OBJECTIVE: To verify whether the capacity of high-density lipoprotein (HDL) to simultaneously receive nonesterified cholesterol, triglycerides, cholesteryl esters, and phospholipids changes with aging and the presence of coronary artery disease. DESIGN: Cross-sectional study with biochemical analyses. SUBJECTS: Eleven elderly patients with coronary artery disease (74±5 years) were compared with the following groups of non-coronary artery disease subjects (referred to as "healthy"): 25 young (25±5 years), 25 middle-aged (42± years), and 25 elderly subjects (75±8 years). METHODS: Plasma samples were incubated with a nanoemulsion labeled with radioactive lipids; the transfer of the lipids from the nanoemulsion to the HDL was measured in chemically precipitated HDL. HDL size and paraoxonase-1 activity were also determined. RESULTS: The transfer of cholesteryl esters and phospholipids to high-density lipoprotein was significantly greater (p<0.001) in healthy elderly subjects than in the middle-aged and younger subjects. Non-esterified cholesterol and triglyceride transfer was not different among these three groups. The HDL size was significantly greater (p<0.001) in healthy elderly subjects than in the middle-aged and younger subjects. The paraoxonase-1 activity was similar among the groups. Compared with healthy elderly subjects, coronary artery disease elderly subjects had significantly less (p<0.05) transfer of non-esterified cholesterol, triglycerides, and cholesteryl esters to the HDL and a significantly smaller (p<0.05) HDL size. CONCLUSION: Because lipid transfer is enhanced in healthy elderly subjects but not in those with coronary artery disease, increasing lipid transfer to HDL may be a protective mechanism against the disease.

Paraoxonase-1 activity, malondialdehyde and glutathione peroxidase in non-alcoholic fatty liver disease and the effect of atorvastatin

The prevalence of non-alcoholic fatty liver disease [NAFLD] appears to be increasing. The aim of the present study was to investigate the relationship between hepatic antioxidant paraoxonase 1 [PON1] activity, lipid peroxidation and antioxidant enzymes in patients with NAFLD and the effect of atorvastatin. This study was conducted on 50 patients with NAFLD and 20 normal subjects matched for age and sex. All of them were subjected to the following investigations: abdominal ultraso-nography, serum PON1 activity level, liver function tests, serum lipid profile, fasting and postprandial blood glucose and serum levels of malondialdehyde [MDA] and glutathione peroxidase [GP]. NAFLD patients were further randomly classified into two groups [25 patients each], groups Ia and Ib. Only group la received atorvastatin 40 mg tablet for 8 months. Obesity, dyslipidaemia and impaired glucose tolerance were prevalent in group I. There was a significant decrease in serum PON1 activity with a significant increase in MDA and GP activity [i.e., there is a significant increase in lipid peroxidation rate] in group I compared with group II. After atorvastatin therapy, there was a significant increase in serum PNO1 activity and significant decrease in serum MDA levels. Patients with NAFLD show enhanced oxidative stress which may lead to non-alcoholic steatohepatitis [NASH]. Reduced PON1 activity and increased MDA could be considered a biochemical marker for lipid peroxidation, which require follow-up in patients with NAFLD. Atorvastatin may have a role in prevention of, or delay, the transformation of liver steatosis into NASH

Determination of serum paraoxonase phenotype distribution by double-substrate method in patients with coronary artery disease

Considering the high incidence of patients with coronary artery disease [CAD] in the Iranian population and a preventive role of serum paraoxonase [PON1] in development of CAD, the present study was designed to determine the distribution of PON1 phenotypes in patients with CAD. A total of 61 patients with coronary stenosis of <50% and 63 patients with coronary stenosis of >70% were included in this study. Paraoxonase and arylesterase activities were measured using paraoxon and phenylacetate as substrate, respectively. Phenotyping of the PON1 Q192R polymorphism was determined by calculating the ratio of salt-stimulated paraoxonase activity to arylesterase activity [double-substrate method]. Patients with stenosis of <50% were separated into three distinct phenotypes at ratios of 2.14 and 5.99 and the population with stenosis of >70% at ratios of 2.42 and 5.91. In patients with stenosis of <50%, PON1 phenotype frequencies were 41% [Q phenotype], 46% [QR phenotype] and 13% [R phenotype]. Frequencies of Q, QR and R phenotypes in patients with stenosis of >70% were 48%, 41% and 11%, respectively. Based on this study and other studies conducted in Iran, it can be concluded that in the Iranian population there is no statistically difference in phenotype distribution of PON1 between patients with CAD [with severe stenosis or mild stenosis] and healthy individuals

Effects of Intronic and Exonic Polymorphisms of Paraoxonase 1 (PON1) Gene on Serum PON1 Activity in a Korean Population

Paraoxonase 1 (PON1) hydrolyzes a number of toxic organophosphorous compounds and reduces lipid peroxide accumulation, and PON1 genetic polymorphisms in the coding region modulate serum PON1 activity. In this study, we investigated the association between 3 polymorphisms of PON1 located in intron 5 (17899insdelTT and 17974CT) and exon 6 (192QR) and serum PON1 activity. The genetic polymorphisms and serum activity of PON1 were analyzed in 153 healthy Koreans by using a direct sequencing assay and spectrophotometric method, respectively. A significant linkage disequilibrium (LD) was observed between all tested single nucleotide polymorphisms, with the strongest LD observed between 17899insdelTT and 192QR (D' = 0.984). The 17899insdelTT, 17974CT and 192QR genetic polymorphisms were associated with significant differences in serum paraoxonase activity. In multiple regression analyses, smoking, triglyceride level, high-density lipoprotein (HDL) level, and the 17899insdelTT and 192QR genetic polymorphisms were significant determinants of serum paraoxonase activity, while age, smoking, triglyceride level, HDL level, and the 192QR genetic polymorphism were significant determinants of serum arylesterase activity. These results suggest that although the 192QR genetic polymorphism in the coding region of PON1 is primarily associated with serum PON1 activity, the intronic polymorphisms are also involved in serum PON1 activity, and this association may be mediated by LD.

Relación entre paraoxonasa, otros componentes de HDL y estado inflamatorio en hemodiálisis / Relation between paraoxonase activity, other HDL components and inflammatory conditions in hemodialyzed patients

La enfermedad renal crónica (ERC) se asocia estrechamente con un estado pro-inflamatorio, aumento de lipoproteínas ricas en triglicéridos y disminución de HDL. La HDL contiene enzimas antioxidantes asociadas como la paraoxonasa (PON), cuya actividad en ERC se encuentra disminuida. Nuestro objetivo fue evaluar la relación entre la actividad de PON, apoA1, colesterol(col)-HDL y Proteína C reactiva-altamente sensible (PCR-as) como marcador de inflamación en pacientes en hemodiálisis. Se estudiaron n = 42 pacientes; edad, mediana (rango) = 50 (25-67) años; sexo M/F = 22/20; antigüedad de hemodiálisis = 4.4 ± 0.5 años; índice de masa corporal (IMC) = 23 ± 0.5 kg/m². Se obtuvo una muestra de sangre después de 12 h de ayuno y se determinaron los parámetros clásicos del perfil lipídico, se midieron los valores de apoproteínas A1 y B, PON a través de su actividad arilesterasa y PCR-as, la cual permitió dividir a los pacientes con PCR-as ≤ 1 (bajo riesgo, rango: 0.1 a 1.0 mg/l) y > 1 mg/l (moderado y alto riesgo, 1.1 a 10.7 mg/l). Los niveles de triglicéridos, col-LDL y apoB no fueron diferentes entre los grupos. Los pacientes con PCR-as > 1 presentaron menor col-HDL (40 ± 2 mg/dl) y apoA1 (118 ± 4 mg/dl) que los pacientes con PCR-as ≤ 1 (50 ± 4 y 133 ± 5, respectivamente); p < 0.05. La PON fue menor en PCR-as > 1: 90.5 ± 24.0 μmol/ml.min que en PCR-as ≤ 1: 105.2 ± 18.0. Consecuentemente, se obtuvieron correlaciones inversas entre apoA1 y PCR-as, r = -0.381 p = 0.013 y entre PON y PCR-as, r = -0.32, p = 0.042. Además, el aumento de PCR-as correlacionó positivamente con el IMC, r = 0.318, p = 0.042. La disminución de col-HDL, apoA1 y PON en los individuos con mayor estado inflamatorio explicaría, en parte, el aumento de riesgo cardiovascular de estos pacientes, dado los efectos antiinflamatorios de la apoA1 y antioxidantes de la PON.

Advanced Chronic Renal Disease (CKD) is closely associated with a pro-inflammatory condition, with an increase in triglyceride-rich lipoproteins and decrease in HDL level. HDL contains antioxidant enzymes such as paraoxonase (PON), whose activity is diminished in CKD. The aim of our study was to evaluate the relationship between PON activity with HDL cholesterol, apo A1 and hs-CRP levels, which are known to be inflammatory markers in hemodialyzed patients. Forty-two patients were studied; age, median (range) = 50 (25-67) years old, gender M/F = 22/20, duration of hemodialysis = 4.4 ± 0.5 years, BMI: 23 ± 0.5 kg/m². After a 12 h fast, a blood sample was obtained and classic components of lipid profile were determined, as well as apoproteins A1 and B, PON by means of its arylsterase activity and hs-CRP levels. On the basis of the latter, patients were divided into two groups: hs-CRP ≤ 1 (low risk, range: 0.1 to 1.0 mg/l) and >1 mg/l (moderate and high risk, 1.1 to 10.7 mg/l). No difference was found in triglycerides, LDL cholesterol and apo B in the groups. Patients with hs-CRP > 1 showed lower HDL cholesterol (40 ± 2 mg/dl) and apo A1 (118 ± 4 mg/dl) than patients with hs-CRP ≤ 1 (50 ± 4 and 133 ± 5, respectively); p < 0.05. PON was lower in hs-CRP > 1 = 90.5 ± 24.0 μmol/ml.min than in hs-CRP ≤ 1 = 105.2 ± 18.0. Consequently, inverse correlations were obtained between apo A1 and hs-CRP, r = -0.381, p = 0.013 and between PON and hs-CRP, r = -0.32, p = 0.042. Furthermore, increase in hs-CRP correlated positively with BMI r = 0.318, p = 0.042. Since apo A1 has an anti-inflammatory role and PON an antioxidant activity, the decrease in HDL and its components, cholesterol, apo A1 and PON, in subjects with higher chronic inflammatory condition might explain, in part, the increased cardiovascular risk in these patients.

Evaluation of serum paraoxonase and arylesterase activities in ankylosing spondylitis patients

OBJECTIVES: The aim of this study was to investigate the activities of serum paraoxonase and arylesterase in patients with ankylosing spondylitis with respect to those of healthy controls, to assess whether these enzyme levels are related to disease activity and functional capacity. METHODS: The study included 32 patients with ankylosing spondylitis whose diagnoses were made according to the modified New York criteria as well as 25 healthy controls matched for age and sex. The Bath Ankylosing Spondylitis Disease Activity Index and the Bath Ankylosing Spondylitis Functional Index were applied to the ankylosing spondylitis patients. As laboratory parameters, the erythrocyte sedimentation rate and serum C-reactive protein level were measured in patients and control subjects. Paraoxonase and arylesterase enzyme activities were measured using appropriate methods. RESULTS: No statistically significant differences (p>0.05) were found between the ankylosing spondylitis patients and controls in terms of serum paraoxonase or arylesterase levels. Furthermore, there was no correlation between clinical and laboratory parameters in patients with ankylosing spondylitis. CONCLUSION: Serum paraoxonase and arylesterase levels in ankylosing spondylitis patients may not differ from those of healthy controls, and there is no significant correlation between antioxidant parameters and the Bath Ankylosing Spondylitis Disease Activity Index or Bath Ankylosing Spondylitis Functional Index scores in ankylosing spondylitis patients. Further research is needed to provide deeper understanding of this disease.

Total oxidant status, total antioxidant status, and paraoxonase and arylesterase activities during laparoscopic cholecystectomy

INTRODUCTION: Laparoscopic cholecystectomy is the gold standard for the treatment of gallstone disease; however, adverse hemodynamic changes induced by increased intraabdominal pressure due to pneumoperitoneum are known to occur. Herein, we investigated the effects of pneumoperitoneum on oxidative stress markers, including paraoxonase, arylesterase, total oxidant status, and total antioxidant status, during laparoscopic cholecystectomy. PATIENTS AND METHODS: Patients that underwent a laparoscopic cholecystectomy were classified as Group I, whereas patients that underwent surgical procedures for an abdominal wall hernia under general anesthesia were classified as Group II. Blood samples were obtained during the preoperative period, the perioperative period, and 24 hours after surgery (postoperative day 1). Leukocyte counts, neutrophil rates, paraoxonase activities, arylesterase activities, and total oxidant and antioxidant status levels were measured. RESULTS: The differences in leukocyte counts and neutrophil rates were not significant between the two groups. In Group I, no significant differences in the total oxidant and antioxidant status levels were identified; however, paraoxonase and arylesterase levels were lower on postoperative day 1. No significant changes were observed in the total oxidant status, total antioxidant status, and paraoxonase or arylesterase activities in Group II. The perioperative total antioxidant status and arylesterase level were higher in Group I in comparison to Group II. CONCLUSION: Paraoxonase and arylesterase levels are useful markers in the evaluation of oxidative stress caused by intraabdominal pressure due to pneumoperitoneum.

Plasma paraoxonase activity in patients with systemic sclerosis.

Background & objectives: Systemic sclerosis (SSc) is a connective tissue disease characterized vascular damage and fi brosis. The aim of this study was to investigate the possible relation between systemic sclerosis and paraoxonase which is an antioxidant enzyme on the HDL. Methods: Twenty nine patients with SSc and 16 healthy subjects (control group) participated in the study. Plasma cholesterol levels, anti-centromere antibody (ACA) levels and paraoxonase (PON) activities were measured. Results: Lower level of high-density lipoprotein (HDL) cholesterol was observed in ACA negative SSc patients than in controls. Paraoxonase activity in ACA positive patients was however found to increase relative to control and ACA negative patient groups. Interpretation & conclusions: Our fi ndings suggested that low HDL level in ACA negative SSc patients might be one of the factors leading to some vascular problems, and increased PON activity in ACA positive SSc group might have some role in the limitation of cutaneous sclerotic process observed in these patients. However, these preliminary fi ndings need to be confi rmed with a larger sample.

Study of paraoxonasel activity and lipid peroxidation in selected male patients with the metabolic syndrome

Today, the metabolic syndrome is one of the major public health concerns as its prevalence increases worldwide with a subsequent predisposition to type 2 diabetes and cardiovascular disease and even mortality. Paraoxonasel [PONI] is a high-density lipoprotein HDL]-associated enzyme capable of hydrolyzing diverse substrates including oxidized phospholipids. The reactive oxygen species induced oxidative stress may play a role in the development of insulin resistance. The oxidative stress causes increased tissue/cellular damage manifested by lipid peroxidation. Was to study PNO1 activity and lipid peroxidation in male patients with the metabolic syndrome. The patients were neither diabetic nor hypertensive apart from mild to moderate hypertension. They were also free from coronary artery disease. 45 male patients the criteria of the metabolic syndrome according to the National Cholesterol Education Program/Adult Treatment Panel III [NCEP] were chosen in the study. They were chosen also to be nondiabetic, nonsmoker, non hypertensive or with mild to moderate degree of hypertension and not suffering coronary artery disease. 15 apparently healthy male, not fulfilling the criteria of the metabolic syndrome and age and culture matched, constituted the control group. All the chosen subjects underwent thorough clinical examination specially measuring waist circumference and the blood pressure. Fasting and postprandial serum glucose. high and low density lipoproteins, serum triglycerides, paraoxonasel activity and malonaldehyde were assayed. Compared with the controls, the patients bad significantly higher level of serum triglycerides, low-density lipoprotein-cholesterol [LDL-C], fasting and postprandial glucose and fasting insulin. There were also significant higher measurements of waist circumference and systolic and diastolic blood pressure. However the patients had lower high density lipoprotein-cholesterol [HDL-C]. They were more insulin resistant as measured by HOMA index. Patients had higher serum malondialdhyde level and lower serum paraoxonasel [PNOl] activity when compared with the controls. There were positive correlations between HOMA index and waist circumference, fasting and postprandial serum glucose, serum triglycerides, serum malondialdhyde level. HOMA index was negatively correlated with HDL-C and PONT activity. There were positive correlations of PONT activity with HDL-C and serum triglycerides and no correlation waist circumference, while there were negative correlation of PONI activity with blood pressure and serum glucose levels. There were negative correlations of PONT activity with HOMA index and serum malondialdhyde level. Serum malondialdhyde level showed positive correlation with waist circumference, blood pressure levels, serum glucose levels, serum triglycerides. Serum malondialdhyde level showed negative correlation with PONT activity and HOMA index. It showed no correlation with HDL-C. Male patients with MetS, who were normotensive or not severely hypertensive and not yet developed DM or cardiovascular complications of MetS, had diminished serum paraoxonasel activity and increased lipid peroxidation. These were correlated with the degree of insulin resistance. These results pointed strongly to increased oxidative stress, The increased oxidative stress along with their atherogenig lipid profile indicated a proatherogenic state. We recommend that clinicians should deal with these hidden factors aiming to avoid MetS complications

Serum arylesterase activity is negatively correlated with inflammatory markers in patients with acute coronary syndromes

To examined whether serum paraoxonase [PON1] and arylesterase [ARE] activities are correlated with inflammatory biomarkers [procalcitonin and high sensitivity C-reactive protein [hs-CRP] in patients with acute coronary syndrome [ACS]. This cross-sectional study was conducted at the Departments of Cardiology and Biochemistry, Uludag University School of Medicine, Bursa, Turkey, from April 2007 to December 2007. Seventy-eight consecutive patients with ACS and 39 healthy controls were investigated. Acute coronary syndrome patients were divided into 3 groups according to their clinical presentation: unstable angina pectoris [UAP] [Braunwald III-B, n=25], non-ST elevation myocardial infarction [NSTEMI] [n=18], and ST-elevation myocardial infarction [STEMI] [n=35]. Serum PON1/ARE activities were measured spectrophotometrically. Levels of procalcitonin and hs-CRP were measured by immunoassay. Paraoxonase/ARE activities were significantly lower in all patient groups compared to controls. No correlation between PON1/ARE activities and high-density-cholesterol levels was seen. Among ACS patients, serum ARE activity correlated inversely with baseline and 48-hour procalcitonin [r=-0.577, p=0.009, and r=-0.642, p=0.019] and hs-CRP levels [r=-0.614, p=0.03, and r=-0.719, p=0.044]. Serum ARE activity is reduced in ACS patients and inversely correlated with inflammatory markers