Paraoxonase-1 is associated with oxidative stress, fibrosis and FAS expression in chronic liver diseases

Ferré, Natàlia; Marsillach, Judit; Camps, Jordi; Mackness, Bharti; Mackness, Michael I.; Riu, Francesc; Coll, Blai; Tous, Mònica; Joven, Jorge

doi:10.1016/j.jhep.2005.12.018

Cited by 87 publications

(58 citation statements)

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“…Gonzalez et al (42) reported that hyperandrogenemia activated and sensitized leukocytes to glucose and increased leukocytic NADPH oxidase P47(phox) subunit gene expression and reactive oxygen species generation in normal-weight PCOS women. The increased oxidative stress was reportedly associated with insulin resistance (43), systemic inflammation, endothelial dysfunction (44,45), stimulated proliferation, testosterone production of theca cells (45,46), and increased hepatic PON1 protein expression (47,48). These findings support our results that the elevated lactonase activities and levels of PON1 might be a compensation for increased oxidative stress and inflammation in PCOS patients.…”

Section: Discussionsupporting

confidence: 88%

“…These findings support our results that the elevated lactonase activities and levels of PON1 might be a compensation for increased oxidative stress and inflammation in PCOS patients. Conversely, PON1 is sensitive to the oxidative stress status which can lead to enzyme inactivation and consumption (49), which may explain the decreased serum PON1 activity and/or levels that are associated with increased PON1 protein expression in some disease statuses (47,48). In brief, PON1 plays an important role in preventing oxidative stress and controlling inflammation, and the absolute or relative lack of PON1 lactonase activity may contribute to PCOS pathology.…”

Section: Discussionmentioning

confidence: 99%

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Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome

Zhang

Liu

et al. 2015

European Journal of Endocrinology

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Objective: To study the relationship between the lactonase activities and status of paraoxonase 1 (PON1) and its association with the PON1 genetic polymorphisms in women with polycystic ovarian syndrome (PCOS). Design: A case-control study. Methods: A total of 455 PCOS patients and 441 control women were included in this study. The lactonase activities and concentrations of PON1 were assayed using 5-thiobutyl butyrolactone (TBBL) and 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase:DEPCyMCase activity. The PON1 genotypes, serum malondialdehyde (MDA) levels and total antioxidant capacity were analyzed. Results: The lactonase activities and levels of PON1 were higher in PCOS patients than in the control women. However, the NLA did not significantly differ between groups. The K108C/T variation of the PON1 gene showed decreased lactonase activities and levels of PON1 in a genotype-dependent manner (CCOCTOTT); the 192Q/R variation of the PON1 gene showed increased PON1 lactonase activities and NLA; and the 55L/M variation of the PON1 gene showed decreased lactonase activities and levels of PON1 but an increased NLA. A multivariable regression analysis showed that the K108C/T, 192Q/R, and 55L/M variations of the PON1 gene, serum apolipoprotein A1, and MDA levels were significant predictors of PON1 lactonase activity, PON1 level, and NLA. Conclusions: The serum lactonase activities and concentrations of PON1 are increased in PCOS patients. The increased oxidative stress and the K108C/T, 192Q/R, and 55L/M genetic polymorphisms of PON1 may be associated with these changes.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome

Zhang

Liu

et al. 2015

European Journal of Endocrinology

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“…In vitro studies showed that RR homozygotes were less effi cient than QQ and QR individuals in protecting lowdensity lipoproteins from copper-induced oxidation ( 44 ). In addition, several case-control studies have reported disease, in which a decreased serum PON1 activity was found to be associated with increased PON1 protein expression ( 13,14 ). Similar results were recently obtained in patients with coronary artery disease ( 38 ).…”

Section: Discussionsupporting

confidence: 57%

“…As expected, patients with HH had signifi cantly higher serum iron and ferritin concentrations, higher transferrin saturation, and lower serum transferrin concentrations than the control group. demonstrated that serum PON1 activity is decreased in patients with chronic hepatocellular liver diseases, despite serum PON1 concentration and hepatic PON1 protein expression being increased (13)(14)(15). More recent evidence indicates that PON1 overexpression provides protection against liver damage ( 16 ).…”

Section: Relationship Between Serum Pon1-related Variables and Other mentioning

confidence: 99%

Paraoxonase-1 status in patients with hereditary hemochromatosis

Martinelli

García-Heredia

Roca

et al. 2013

Journal of Lipid Research

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“…Aging and pathologic states such as renal disease, diabetes mellitus, cardiovascular disease, and liver cirrhosis are associated with decreased PON1 activity, and various dietary and lifestyle factors have been reported to influence serum PON1 activity Paragh et al 1998Paragh et al , 1999Mackness and Durrington, 1995;Ferré et al 2006). Smoking has been associated with reduced PON1 activity and concentrations in patients with coronary artery disease.…”

Section: Association Of Adipokines and Pon1 Activity In Childhood Obementioning

confidence: 99%

Alteration of PON1 Activity in Adult and Childhood Obesity and Its Relation to Adipokine Levels

Serés

Bajnok

Harangi

et al. 2009

Advances in Experimental Medicine and Biology

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Obesity as a pathogenic disorder is a predisposing factor for cardiovascular diseases and shows an increasing incidence in the industrialized countries. Adipokines such as leptin, adiponectin and resistin have a great impact on the development of atherosclerosis in obesity. Elevated levels of leptin have been found to be atherogenic whereas decreased levels of adiponectin have been proved to be anti-atherogenic in recent studies. The exact role of resistin in the process of atherosclerosis has so far remained uncertain and controversial. In our recent work, we studied the alteration in human paraoxonase-1 (PON1) activity and adipokine levels; furthermore, we also aimed at identifying the potential correlation between these parameters in this metabolic disorder. We investigated the abovementioned parameters both in adults and in children, with regard to the emerging role of childhood obesity and to get a clearer view of these factors during a whole lifetime. Investigating the adult population with a broad range of body mass index (BMI) we found significantly increased leptin and significantly decreased adiponectin and resistin levels and PON1 activity in the obese group compared to the lean controls. Adiponectin and resistin levels showed significantly positive correlation, while leptin and BMI showed significantly negative correlation with PON1 activity.Our findings were similar in childhood obesity: leptin showed significantly negative correlation, while adiponectin showed significantly positive correlation with PON1 activity. We found gender differences in the univariate correlations of leptin and adiponectin levels with PON1 activity in the adult population. In multiple regression analysis, adiponectin proved to be an independent factor of PON1 activity both in childhood and adult obesity, furthermore thiobarbituric acid-reactive substances (TBARS) also proved to be an independent predictor of the enzyme in adults, reflecting the important role of oxidative stress in obesity. Investigating PON 192 Q/R polymorphism by phenotypic distribution (A/B isoenzyme) in obese children, we found a significant correlation of PON1 arylesterase activity with leptin and adiponectin levels, and of body fat percentage with PON1 192 B isoenzyme.According to our studies, these metabolic changes in obesity predispose to the early development of atherosclerosis throughout our whole lifetime. Decreased activity of PON1 and alterations in adipokine levels in childhood obesity could contribute to an early commencement of this process, detected only later in adulthood by increased cardiovascular morbidity and mortality. Changed levels of leptin, adiponectin, resistin and PON1 activity at all ages, just like 192 Q/R polymorphism determined by phenotypic distribution, may be useful markers beside the general risk factors.Keywords (separated by '-') Adipokines -Leptin -Adiponectin -Resistin -Obesity -Paraoxonase-1 -Childhood Abstract Obesity as a pathogenic disorder is a predisposing factor for cardiovascular diseases and shows a...

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Paraoxonase-1 is associated with oxidative stress, fibrosis and FAS expression in chronic liver diseases

Cited by 87 publications

References 43 publications

Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome

Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome

Paraoxonase-1 status in patients with hereditary hemochromatosis

Alteration of PON1 Activity in Adult and Childhood Obesity and Its Relation to Adipokine Levels

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