Studies on HDL associated enzymes under experimental hypercholesterolemia: possible modulation on selenium supplementation

Abstract

BackgroundAtherosclerosis is a chronic disorder of the arterial wall that starts by formation of fatty streaks and gradually evolves into atherosclerotic plaques. High-density lipoproteins (HDL) blood levels are inversely correlated with atherosclerosis. This beneficial effect of HDL has been partly attributed to its antioxidant properties mediated by paraoxonase1 (PON1) or platelet-activating factor acetylhydrolase (PAF-AH). The present study was aimed to study HDL associated enzymes i.e. PON1 and PAF-AH under experimental hypercholesterolemia and their possible modulation on selenium (Se; an antioxidant) supplementation. Male Sprague Dawley rats were divided into three groups and fed on the control diet, high fat diet (HFD) and HFD + Se respectively for the period of 4 months.ResultsCholesterol, triglycerides, HDL and LDL levels were significantly increased by HFD feeding. Selenium supplementation lowered the triglyceride level, whereas the other lipid values remained unchanged. Serum selenium levels were reduced by 31% and ROS levels in the liver were 2-fold increased by HFD. Se supplementation, however, diminished the HFD-induced ROS levels by 29%. Furthermore, Se also improved the HFD-mediated reduction of serum PON1 enzyme activity by 34% and PON1 protein levels by 21%. However, no significant effect of Se was detected on the reduced PAF-AH proteins levels in HFD fed rats. mRNA expression of PON1 and PAF-AH in the liver was not affected in the Se treated groups.ConclusionSe supplementation appears to be protective in hypercholesterolemia by restoring the antioxidant properties of the HDL associated enzyme i.e. PON1 whereas biological system aims towards maintaining the same PAF-AH levels even on selenium supplementation indicating its probable role in both anti and pro-atherogenic activities. Therefore, Se supplementation might be a valuable approach to limit the adverse effects of hypercholesterolemia and may need further investigations.

Dietary antioxidants (selenium and N-acetylcysteine) modulate paraoxonase 1 (PON1) in PCB 126-exposed rats

“…The marginal effect of PCB 126 on LDL-C, consistent with other reports (Lind et al 2004), resulted in an increase in the HDL-C/LDL-C ratio which should be protective against cardiovascular disease if not disturbed otherwise, for example by oxidative stress. Se had no consistent effect on serum lipids, which is in agreement (Chen et al 1986; Crespo et al 1995; Panczenko-Kresowska and Ziemlanski 1987) or disagreement (Bleys et al 2008; Kaur and Bansal 2009; Qu et al 2000; Stranges et al 2010) with other reports. Differences in Se concentration and duration of feeding may be accountable for these discrepancies, since only a low Se level may increase the ‘good cholesterol’, while too much Se will elevate TC, LDL-C, and HDL-C (Laclaustra et al 2009b), and increase the risk of cardiovascular diseases (Laclaustra et al 2009a; Stranges et al 2010).…”

“…Although this change in PON1 should enhance protection against cardiovascular diseases, PCB 126 was linked to increased risk for atherosclerosis (Hennig et al 2002a; Hennig et al 2002b). PCB 126 also disrupted the homeostasis of antioxidants such as selenium (Hassan et al 1985; Lai et al 2011; Stemm et al 2008), an element that appears to be protective for high-density lipoprotein (HDL)-associated enzymes like PON1 (Kaur and Bansal 2009). In addition, PCB 126 depleted GSH (Hassoun and Periandri-Steinberg 2010) which may place the free –SH group in PON1 at increased risk of oxidation.…”

Effect of walnut-enriched meat on the relationship between VCAM, ICAM, and LTB4 levels and PON-1 activity in ApoA4 360 and PON-1 allele carriers at increased cardiovascular risk

“…The significant relationships found between the changes in PON-1 activity and LTB4 and those of soluble adhesion molecule levels, suggest that this enzyme has an additional role. PON-1 works as a systemic antioxidant (Kaur and Bansal, 2009;Lakshmy et al, 2010), helps to maintain the activities and concentrations of other endogenous antioxidants (for example, superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase) (unpublished data), and to decrease chemoattractants and inflammatory molecules, as has been shown in the present paper. Gene-diet interactions may be responsible for the differences found in study participants.…”

Regulation of paraoxonase 1 (PON1) in PCB 126-exposed male Sprague Dawley rats

“…With the high dose or long time exposure both total and HDL-C levels were significantly decreased compared to the low dose or 1 week exposure, probably because the hepatic synthesis of cholesterol was impaired due to liver damage. The increase in total cholesterol, mediated by elevation of HDL-C, commonly known as ‘good cholesterol’, could be beneficial with respect to cardiovascular disease and atherosclerosis due to its association with PON1 (Aviram, 2006; Kaur and Bansal, 2009; Ferretti et al , 2010). …”