Evaluation of Lipid metabolizing enzymes: Paraxonase1(PON1) and Lecithin Cholesterol acyltransferase (LCAT) activities in children with nephrotic syndrome

Authors

  • Raghad Jamal Ali Ministry of Health, Baghdad Medical City, Baghdad, Iraq
  • Rayah Sulaiman Baban Department of Chemistry and Biochemistry, College of Medicine, Al- Nahrain University, Baghdad, Iraq
  • Shatha Hussain Ali Department of Pediatrics, College of Medicine, Al- Nahrain University, Baghdad, Iraq

DOI:

https://doi.org/10.47419/bjbabs.v2i01.38

Keywords:

Lipid metabolizing enzymes, Paraxonase1, PON1, Lecithin Cholesterol acyltransferase, LCAT, Nephrotic Syndrome, Fluorescence assay

Abstract

Background: The most common glomerular disorder in children is nephrotic syndrome, associated with high morbidity despite notable advances in its treatment. Many of the nephrotic syndrome complications, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidemia. Paraoxonase enzyme is responsible for the most of antioxidant properties of HDL, thus preventing the formation of atherogenic ox-LDL molecules, and Lecithin Cholesterol acyltransferase is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport pathway, which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion.

Objective: The present study aimed to investigate the serum activities of paraoxonase-1(PON-1) and lecithin cholesterol acyltransferase (LCAT) in children with nephrotic syndrome in an active phase (as newly diagnosed or old cases with acute relapse)

 also, to study any correlation exists between paraoxonase-1 activity and lipid profile.

Methods: This study consists of Group 1 with 40 cases of nephrotic syndrome in the age group of (2-14 years) and Group 2 with 40 age and sex-matched healthy controls. Lipid profile and paraoxonase activity, Lecithin Cholesterol acyltransferase activities were measured in both groups' serum samples.

 Results: Statistical analysis by student's t-test showed that the mean levels of Total Cholesterol, Triglycerides, LDL were significantly increased in Group 1 when compared to Group 2 (p <0.001). PON1 and Lecithin Cholesterol acyltransferase levels were significantly lowered in Group 1 compared to Group 2, and there is no significant difference among nephrotic groups.

Conclusion: Both Paraoxonase-1 enzyme and Lecithin Cholesterol acyltransferase are considered good promising predictors for nephrotic syndrome and other parameters such as LDL, HDL, and T.G. The significantly decreased Paraoxonase-1 enzyme and Lecithin Cholesterol acyltransferase activities result in increased oxidation of LDL, thus accelerating atherosclerosis.

Downloads

Download data is not yet available.

References

Niaudet P, Boyer O. Idiopathic Nephrotic Syndrome in Children: Clinical Aspects. In: E A, and Niaudet P HW, N Y, F E, S G, editors. Pediatric Nephrology. Springer,Berlin, Heidelberg; 2016. p. 839–882. Available from: https://doi.org/10.1007/978-3-662-43596-0_24.

Gbadegesin R, Smoyer WE. Nephrotic Syndrome. In: Geary DF, Schaefer F, editors. Comprehensive Pediatric Nephrology; 2008. p. 205–218. chapter 12.

Mansour SA, Neemat-Allah MAA, Shal ASE, Ibrahim SSAEA. The Value of Estimating Paraoxonase Activity in Nephrotic Children. The Egyptian Journal of Hospital Medicine . 2020;80(2):852–856. Available from: 10.12816/EJHM.2020.100200.

Kowalska K, Socha E, Milnerowicz H. The role of paraxonase in cardiovascular disease. Annals of Clinical and Laboratory Science. 2015;45(2):226–233.

Milaciu MV, S, tefan Cristian Vesa, Bocs,an IC, Ciumărnean L, Sâmpelean D, Negrean V, et al. Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease. Journal of Clinical Medicine. 2019;8(12):2200–2200. Available from: 10.3390/jcm8122200;https://dx.doi.org/10.3390/jcm8122200

Dias CG, Batuca JR, Marinho AT, Caixas U, Monteiro EC, Antunes AMM, et al. Quantification of the arylesterase activity of paraoxonase-1 in human blood. Anal Methods. 2014;6(1):289–294. Available from: 10.1039/c3ay41527a;https://dx.doi.org/10.1039/c3ay41527a.

Franceschini G, Maderna P, Sirtori CR. Reverse cholesterol transport: Physiology and pharmacology. Atherosclerosis. 1991;88(2-3):99–107. Available from: 10.1016/0021-9150(91)90073-c;https://dx.doi.org/10.1016/0021-9150(91)90073-c.

Rosenson RS, Brewer HB, Davidson WS, Fayad ZA, Fuster V, Goldstein J, et al.Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation. 2012;125(15):1905–1919. Available from: 10.1161/CIRCULATIONAHA.111.066589.

Czarnecka H, Yokoyama S. Regulation of Cellular Cholesterol Efflux by Lecithin:Cholesterol Acyltransferase Reaction through Nonspecific Lipid Exchange. Journal of Biological Chemistry. 1996;271(4):2023–2028. Available from: 10.1074/

jbc.271.4.2023;https://dx.doi.org/10.1074/jbc.271.4.2023

Adimoolam S, A J. Identification of a domain of lecithin-cholesterol acyltransferase that is involved in interfacial recognition. Biochem Biophys Res Commun.1997;232(3):783–787. Available from: 10.1006/bbrc.1997.6375

Rousset X, Shamburek R, Vaisman B, Amar M, Remaley AT. Lecithin Cholesterol Acyltransferase: An Anti- or Pro-atherogenic Factor? Current Atherosclerosis Reports. 2011;13(3):249–256. Available from: 10.1007/s11883-011-0171-6;https:

//dx.doi.org/10.1007/s11883-011-0171-6

Calabresi L, Simonelli S, Gomaraschi M, Franceschini G. Genetic lecithin:cholesterol

acyltransferase deficiency and cardiovascular disease. Atherosclerosis.

;222(2):299–306. Available from: 10.1016/j.atherosclerosis.2011.11.034;https:

//dx.doi.org/10.1016/j.atherosclerosis.2011.11.034.

Levison SS, Wagner SG. Implications of reverse cholesterol transport: recent studies.

Clin Chim Acta. 2015;439:154–161. Available from: 10.1016/j.cca.2014.10.018.

Ossoli A, Simonelli S, Vitali C, Franceschini G, Calabresi L. Role of LCAT in

Atherosclerosis. Journal of Atherosclerosis and Thrombosis. 2016;23(2):119–127.

Available from: 10.5551/jat.32854;https://dx.doi.org/10.5551/jat.32854.

paraoxonase 1 Activity Assay Kit (ab241044) Abcam, Japan. Version 1 Last updated

th; 2018. Available from: https://www.abcam.com/paraoxonase-1-activity-assaykit-ab241044.html.

LCAT Activity Assay Kit 1. (ab242306) - Abcam, Japan. Version 1 Last updated

th; 2018. Available from: https://www.abcam.com/ps/products/242/ab242306/

documents/ab2.

IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp; 2019

El-Melegy NT, Mohamed NA, Sayed MM. Oxidative Modification of LowDensity Lipoprotein in Relation to Dyslipidemia and Oxidant Status in Children

With Steroid Sensitive Nephrotic Syndrome. Pediatric Research. 2008;63(4):404–

Available from: 10.1203/pdr.0b013e3181647af5;https://dx.doi.org/10.1203/

pdr.0b013e3181647af5.

zewska MHK, Obuchowicz AK, Wielkoszyński T, Zmudzińska Kitczak J, Urban K,

Hyla-Klekot L. Evaluation of certain constituents of antioxidant defense in youth

treated in the past for steroid-sensitive idiopathic nephrotic syndrome. Pediatric

Nephrology. 2009;24(11):2187–2192. Available from: 10.1007/s00467-009-1269-8;

https://dx.doi.org/10.1007/s00467-009-1269-8.

Hu P, Lu L, Hu B, Du PF. Characteristics of lipid metabolism under different urinary

protein excretion in children with primary nephrotic syndrome. Scandinavian Journal of Clinical and Laboratory Investigation. 2009;69(6):680–686. Available from:

3109/00365510902980751;https://dx.doi.org/10.3109/00365510902980751

Vijayetha P, Patil1 AB, Patil2, Vidya S, Patil3, Deepti G. Ingleshwar: Paraoxonase

Activity and Lipid Profile in Paediatric Nephrotic Syndrome: A Cross-sectional.

Study Journal of Clinical and Diagnostic Research. 2016;10(3):17–20

Nishi S, Ubara Y, Utsunomiya Y, Okada K, Obata Y, Kai H, et al. Evidence-based

clinical practice guidelines for nephrotic syndrome 2014. Clinical and Experimental

Nephrology. 2016;20:342–370. Available from: 10.1007/s10157-015-1216-x;https:

//dx.doi.org/10.1007/s10157-015-1216-x.

Al-Assadi AB, Mohammed NA, Ali SH. SERUM IMMUNOGLOBULING, M AND

A LEVELS IN CHILDREN WITH NEPHROTIC SYNDROME AND ITS CORRELATION WITH BIOCHEMICAL PARAMETERS. Pakistan Journal of Biotechnology. 2018;15(4):1011–1016.

Dobiasova M. Atherogenic Impact of Lecithin-Cholesterol Acyltransferase

and Its Relation to Cholesterol Esterification Rate in HDL (FERHDL) and AIP

[log(TG/HDL-C)] Biomarkers: The Butterfly Effect? . PHYSIOLOGICAL

RESEARCH. 2017;66(2):193–203. Available from: 10.33549/physiolres.933621

Eroglu E, Kocyigit I, Unal A, Korkar H, Karakukcu C, Orscelik O, et al. Serum

paraoxonase activity is associated with epicardial fat tissue in renal transplant recipients. International Urology and Nephrology. 2015;47(8):1409–1414. Available from:

1007/s11255-015-1051-8;https://dx.doi.org/10.1007/s11255-015-1051-8.

Yokoyama S, Fukushima D, Kupferberg JP, Kézdy FJ, Kaiser ET. The mechanism

of activation of lecithin:cholesterol acyltransferase by apolipoprotein A-I and an

amphiphilic peptide. Journal of Biological Chemistry. 1980;255(15):7333–7339.

Available from: 10.1016/s0021-9258(20)79708-5;https://dx.doi.org/10.1016/s0021-

(20)79708-5.

Parks JS, Huggins KW, Gebre AK, Burleson ER. Phosphatidylcholine fluidity

and structure affect lecithin:cholesterol acyltransferase activity. Journal of Lipid

Research. 2000;41(4):546–553. Available from: 10.1016/s0022-2275(20)32402-0;

https://dx.doi.org/10.1016/s0022-2275(20)32402-0

Ece A, Atamer Y, Gürkan F, Davutoğlu M, Koçyiğit Y, Tutanç M. Paraoxonase, total

antioxidant response, and peroxide levels in children with steroid-sensitive nephrotic

syndrome. Pediatric Nephrology. 2005;20(9):1279–1284. Available from: 10.1007/

s00467-005-1956-z;https://dx.doi.org/10.1007/s00467-005-1956-z.

Rozek LS, Hatsukami TS, Richter RJ, Ranchalis J, Nakayama K, McKinstry LA,

et al.. The correlation of paraoxonase (PON1) activity with lipid and lipoprotein

levels differs with vascular disease status. Elsevier BV; 2005. Available from:

1194/jlr.m400489-jlr200;https://dx.doi.org/10.1194/jlr.m400489-jlr200.

Downloads

Published

2021-05-05

How to Cite

Raghad Jamal Ali, Rayah Sulaiman Baban, & Shatha Hussain Ali. (2021). Evaluation of Lipid metabolizing enzymes: Paraxonase1(PON1) and Lecithin Cholesterol acyltransferase (LCAT) activities in children with nephrotic syndrome. Baghdad Journal of Biochemistry and Applied Biological Sciences, 2(01), 47–58. https://doi.org/10.47419/bjbabs.v2i01.38

Issue

Section

Research articles