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Extensive research has been carried out to understand and elucidate the mechanisms of paraoxonase 1 (PON1) in the development of diseases including cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. This review focuses on the relationship between PON1 and cancer. The data suggest that PON1, oxidative stress, chronic inflammation, and cancer are closely linked. Certainly, the gene expression of PON1 will remain challenging to study. Therefore, targeting PON1, redox-sensitive pathways, and transcription factors promise prevention and therapy in the development of several diseases, including cancer.

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Paraoxonase 1 (PON1) is a calcium-dependent esterase synthesized primarily in the liver and secreted into the plasma where it is associated with high-density lipoproteins (HDL). PON1 hydrolyzes and detoxifies some toxic metabolites of organophosphorus compounds (OPs) such as methyl parathion and chlorpyrifos. Thus, PON1 activity and expression levels are important for determining susceptibility against OPs poisoning. Some studies have demonstrated that OPs can modulate gene expression through interactions with nuclear receptors. In this study, we evaluated the effects of methyl parathion and chlorpyrifos on the modulation of PON1 in Human Hepatocellular Carcinoma (HepG2) cells by real-time PCR, PON1 activity assay, and western blot. The results showed that the treatments with methyl parathion and chlorpyrifos decreased PON1 mRNA and immunoreactive protein and increased inflammatory cytokines in HepG2 cells. The effects of methyl parathion and chlorpyrifos on the downregulation of PON1 gene expression in HepG2 cells may provide evidence of OPs cytotoxicity related to oxidative stress and an inflammatory response. A decrease in the expression of the PON1 gene may increase the susceptibility to OPs intoxication and the risk of diseases related to inflammation and oxidative stress. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 490-500, 2017.

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Introduction: Serum paraoxonase 1 (PON1) is now known to be related to cardiovascular diseases (CVD). The aim of this study was to determine the relationship between PON1 concentration and high-density lipoprotein (HDL) subclasses in patients with proven CVD, cardiovascular risk factors but no CVD (CRF), and in healthy controls (control group). Material and methods: A case-control study was carried out with 69 volunteers from the Mexican Institute of Social Security, Mexico. Clinical parameters, lipid profile, PON1 concentration, PON1 activities (AREase and CMPAase), and HDL subclasses were evaluated. Results: Patients with CVD had significantly higher glucose and lower total cholesterol than the control group had (p < 0.01). AREase activity was not different between the control (122.57 ±30.72 U/ml), CRF (115.81 ±32.81 U/ml), and CVD (109.34 ±29.60 U/ml) groups. PON1 concentration was significantly lower in CVD patients than in CRF and control patients (p < 0.001); a positive correlation was observed between AREase activity and PON1 concentration in the CVD group (Rho = 0.58; p < 0.01). Logistic regression analysis showed that the decrease in PON1 level was associated with the CVD group (RRR = 0.20; 95% CI: 0.09-0.45) but not with the CRF group (RRR = 1.29; 95% CI: 0.89-1.90). Significant differences were observed in HDL 2a and HDL 3a concentrations between the control group and CRF and CVD groups (p < 0.05), but not between the CRF and CVD groups. Conclusions: Our data suggest that PON1 status and HDL characteristics could be early biomarkers that predict the potential for developing CVD.

Paraoxonase 1 (PON1) plays a role as antioxidant on HDL. Including in diet additionally ingest of polyphenolic compounds can stimulate PON1 transcription and increase its activity. The aim of this study was to evaluate the effect of dietary intake, red wine consumption, and PON1 genotypes (Q192R, L55M and C-108T) on the specific activity of PON1 in a healthy population. A descriptive and analytical pilot study was conducted in Mexican volunteers clinically healthy (n = 45) aged from 21–59 years. Over 6 weeks, the study participants ingested 120 mL of red wine per day. PON1 concentration, PON1 activities, genetic polymorphisms and dietary intake were evaluated. The preliminary fingerprinting of the wine was determined to corroborate the presence of phenolic compounds such as tannins and gallotannins. Neither dietary intake nor PON1 genotypes showed an effect on the specific activity of PON1. However, a significant increase in specific AREase activity after red wine consumption period was observed in the study participants. Our data suggest that the moderate consumption of red wine has a beneficial effect on PON1 specific AREase activity in this healthy Mexican population.