Paraoxonase 1 (PON1) is a hydrolytic enzyme with wide range of substrates, and capability to protect against lipid oxidation. Despite of the large number of compounds that can be hydrolyzed by paraoxonase, the biologically relevant substrates are still not clearly determined. There is a massive in vitro and in vivo data to demonstrate the beneficial effects of PON1 in several atherosclerosis-related processes. The enzyme is primarily expressed in liver; however, it is also localized in other tissues. PON1 attracted significant interest as a protein that is responsible for the most of antioxidant properties of high-density lipoprotein (HDL). Several bioactive molecules such as dietary polyphenols, aspirin and its hydrolysis product salicylate, are known to stimulate PON1 transcription activation in mouse liver and HepG2 cell line. Studies on the activity, function, and genetic makeup have revealed a protective role of PON1. Some striking data were obtained in PON1 gene knockout and PON1 transgenic mouse models and in human studies. The goal of this review is to assess the current understanding of PON1 expression, enzymatic and antioxidant activity, and its atheroprotective effects. Results from in vivo and in vitro basic studies; and from human studies on the association of PON1 with coronary artery disease (CAD) and ischemic stroke will be discussed.

Circulating cytokine levels were influenced by ovarian stimulation, as demonstrated by increased levels of IL-6, MCP-1 and PON-1, and decreased level of TNF-α at the end of controlled ovarian stimulation. While evidence of relationship between circulating cytokines with mild endometriosis was not found, PCOS was associated with elevated serum IL-6 and MCP-1 but lower TNF-α concentration. Unexplained infertility was associated with elevated TNF-α level. No relationship between serum PON-1 concentration and PCOS, mild endometriosis or unexplained infertility was noted.

Study objectivesWe proposed that mice supplemented with quercetin, a class of flavonoids known to have antioxidant and anti-inflammatory properties, will have profound effects on the pathophysiology of atherosclerosis when combined with exercise.Study designForty C57BL6 LDLr −/− mice were divided into four groups (n = 10): control untreated (NN); control group supplemented with 100 μg/day of quercetin (NQ); exercise group (EN); and exercise group supplemented with 100 μg/day of quercetin (EQ). All animals were fed atherogenic diet. The exercise groups were run on a treadmill for 30 minutes, 15 m/min for 5 days/week for 30 days. After 30 day animals were sacrificed and tissues were harvested.Results and conclusionMice supplemented with quercetin during exercise sessions had 78% atherosclerotic plaque reduction compared to control mice and 40% less atherosclerotic plaque formation compared to control group supplemented with quercetin. The manifestation of the combination of quercetin supplementation with exercise was more evident in the pro-reverse cholesterol transport genes, indicating a plausible mechanism for their combined beneficial effect.The pathogenesis of atherosclerosis, the major cause of cardiovascular diseases (CVD), is multifactorial and therefore its treatment approaches and the ability to regress the plaque are complicated. Data from research on animal models and clinical studies have indicated that moderate daily exercise can alleviate the risk for the development of atherosclerotic plaques, while the same has not been true for the supplementation of antioxidants.

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Introduction Triglyceride (TG) is an independent risk factor for coronary heart disease. Previous work has shown that short-term supplementations of mouse chow with oxidized linoleic acid (OxLA) significantly reduce the level of plasma triglycerides. Study Objective This study aims to determine the effects of longer-term supplementation of mouse chow with various concentrations of oxidized linoleic acid (OxLA) on plasma triglycerides. Study Design The study consisted of forty C57BL/6 wildtype mice divided into four groups (n = 10). Two groups were kept as controls. One control group (P) was fed plain chow and the second control group (C) was fed chow supplemented with linoleic acid. The other two experimental groups (A) and (B) were fed oxidized linoleic acid supplemented chow in the following doses: 9 mg/day of oxidized linoleic acid and 18 mg/day of oxidized linoleic acid/mouse. Results and Conclusion Mice that were on a diet supplemented with the higher dose of oxidized linoleic acid showed a 39% decrease in hepatic PPAR-α and a significant decrease in the plasma HDL levels compared to the mice that were fed diets of plain and linoleic acid supplemented chow. Interestingly, the longer-term consumption of oxidized linoleic acid may predispose to atheropathogenesis.

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NF‐kB belongs to a family of structurally related inducible transcription factors known to be activated in the vessel wall in atherosclerosis and other diseases NF‐kB activation is mediated by diverse extracellular signals including oxidized LDL, and inflammatory cytokines. In the current study we combined quercetin and exercise to examine the effect of the combination.Study Design and MethodsWe investigated the combination of exercise and quercetin intake in C57BL6 normal male mice fed normal mouse chow. Mice were divided into four groups. These groups are as follows: Control mice, left untreated; control quercetin group, orally supplied with 100 μg/day of quercetin without exercising; exercise group without quercetin, and exercise group with quercetin supplements. The exercise groups were run on a treadmill for 30 minutes, 30m/m/ 5 days/week for 60 days. At the end of the study, mice were sacrificed tissues such as the aorta, adipose and livers were collected for gene expressions for genes associated with NFkB signaling, inflammation, and lipoprotein metabolism were analyze.Results and DiscussionNFkB mRNA levels was significantly (P<0.05) upregulated with the combination of exercise and quercetin intake, however on the other hand exercise or quercetin intake alone have resulted in significant (P<0.05) down regulation of its mRNA levels.ConclusionThis study demonstrated that quercetin intake with exercise modulate NFkB signaling and its associated genes.

Atherosclerosis is a chronic disease of the large arteries; mostly attributed to oxidative stress and inflammation. This results in arterial heart disease, and stroke. Animal studies using a variety of antioxidants strongly suggest that antioxidants may protect against cardiovascular disease (CVD). Paradoxically, exercise which induces a severe oxidative stress resulting in the depletion of plasma and tissue antioxidants is an important deterrent of CVD. We propose that quercetin a flavonoid will have profound effects on the pathophysiology of atherosclerosis if combined with exercise by inhibiting lipids oxidation, promoting clearance and improving the acute exercise induced oxidative stress resulting in lowering cholesterol, artery lipids deposition and plaque regression. This study tested the possible beneficial effects of the combined exercise and quercetin on modulators of oxidation and inflammation in C57BL6 LDL –/– mice fed atherogenic diet. 40 mice were divided into four groups (10 each). These are: Control mice, left untreated; quercetin group, orally supplied with 100 ug/day of quercetin; exercise group, exercised in a treadmill for 30 minutes, 15 m /min; and the exercise and quercetin group which received quercetin and exercise dose similar to the respective groups. All animals were on atherogenic diet. The treatments were provided 5 days/week for 30 days. At the end of the month of treatment, mice were sacrificed, and atherosclerotic lesions in aorta were quantified. Liver, aorta and adipose tissue gene expressions for genes associated with oxidative stress, inflammation and lipoproteins were analyzed. The above figure shows the differences in atherosclerotic plaque formations between groups. However in addition to the changes seen between the groups as the result of quercetin and exercise treatment; one of the most Intriguing findings, is the significant (P<0.001) drop in mice body weigh associated with the combined quercetin and exercise treatment compared to control.