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Studies on HDL associated enzymes under experimental hypercholesterolemia: possible modulation on selenium
Harman D Kaur1, Mohinder P Bansal
1Department of Biophysics, Panjab University, Chandigarh 160014, India. dayalharman@yahoo.com
Insights
Selenium supplementation may protect against hypercholesterolemia by restoring paraoxonase1 (PON1) antioxidant properties. This highlights selenium
Area of Science:
- Biochemistry
- Nutritional Science
- Cardiovascular Research
Background:
- Atherosclerosis is a chronic arterial disease characterized by plaque formation.
- High-density lipoproteins (HDL) possess antioxidant properties, partly via paraoxonase1 (PON1) and platelet-activating factor acetylhydrolase (PAF-AH).
- Experimental hypercholesterolemia in rats was induced using a high-fat diet (HFD).
Purpose of the Study:
- To investigate HDL-associated enzymes PON1 and PAF-AH in experimental hypercholesterolemia.
- To evaluate the modulatory effects of selenium (Se) supplementation on these enzymes.
Main Methods:
- Male Sprague Dawley rats were divided into three groups: control, HFD, and HFD + Se.
- Dietary interventions lasted for 4 months.
- Lipid profiles, serum selenium, reactive oxygen species (ROS) levels, PON1 and PAF-AH activities/protein levels, and hepatic mRNA expression were assessed.
Main Results:
- HFD significantly increased cholesterol, triglycerides, HDL, and LDL. Se supplementation reduced triglycerides but did not alter other lipid values.
- HFD elevated hepatic ROS levels and reduced serum PON1 activity and protein. Se supplementation diminished ROS and improved PON1 activity and levels.
- Se did not significantly affect PAF-AH protein levels or the hepatic mRNA expression of PON1 and PAF-AH in HFD-fed rats.
Conclusions:
- Selenium supplementation demonstrates a protective effect in hypercholesterolemia, primarily by restoring the antioxidant function of HDL-associated PON1.
- The biological system appears to maintain PAF-AH levels despite selenium supplementation, suggesting complex roles in atherogenesis.
- Selenium supplementation may be a valuable strategy to mitigate hypercholesterolemia's adverse effects, warranting further investigation.
Background:
Atherosclerosis 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.
Results:
Cholesterol, 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.
Conclusion:
Se 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.
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