Evaluation of lipid metabolizing enzymes: Paraxonase1 (PON1) and lecithin cholesterol acyltransferase (LCAT) activities in children with nephrotic syndrome

Authors

  • Raghad J. Ali Ministry of Health, Baghdad Medical City, Baghdad, Iraq
  • Rayah S. Baban Department of Chemistry and Biochemistry, College of Medicine, Al-Nahrain University, Baghdad, Iraq
  • Shatha H. Ali Department of Pediatrics, College of Medicine, Al-Nahrain University, Baghdad, Iraq

DOI:

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

Keywords:

fluorescent assay, lecithin cholesterol acyltransferase, nephrotic syndrome, PON1, LCAT

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 the 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.

Objectives: 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 of 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 lower in group 1 compared to group 2, and there is no significant difference among nephrotic groups.

Conclusions: Both paraoxonase-1 enzyme and lecithin cholesterol acyltransferase are considered good promising predictors for nephrotic syndrome and other parameters such as LDL, HDL, and TG. The significantly decreased paraoxonase-1 enzyme and lecithin cholesterol acyltransferase activities result in increased oxidation of LDL, thus accelerating atherosclerosis.

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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. DOI: 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. DOI: https://doi.org/10.1016/B978-0-323-04883-5.50018-0

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. DOI: https://doi.org/10.21608/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 DOI: https://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. DOI: https://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. DOI: https://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. DOI: https://doi.org/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 DOI: https://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 DOI: https://doi.org/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 DOI: https://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. 2012;222(2):299–306. Available from: 10.1016/j.atherosclerosis.2011.11.034;https: //dx.doi.org/10.1016/j.atherosclerosis.2011.11.034. DOI: https://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. DOI: https://doi.org/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. DOI: https://doi.org/10.5551/jat.32854

paraoxonase 1 Activity Assay Kit (ab241044) Abcam, Japan. Version 1 Last updated 29th; 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 13th; 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):404–409. Available from: 10.1203/pdr.0b013e3181647af5;https://dx.doi.org/10.1203/pdr.0b013e3181647af5. DOI: https://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/s00467-009-269-8.

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: 10.3109/00365510902980751;https://dx.doi.org/10.3109/00365510902980751 DOI: https://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. DOI: https://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 DOI: https://doi.org/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: 10.1007/s11255-015-1051-8;https://dx.doi.org/10.1007/s11255-015-1051-8. DOI: https://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 anamphiphilic 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/s0021-9258(20)79708-5. DOI: https://doi.org/10.1016/S0021-9258(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 DOI: https://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. DOI: https://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: 10.1194/jlr.m400489-jlr200;https://dx.doi.org/10.1194/jlr.m400489-jlr200. DOI: https://doi.org/10.1194/jlr.M400489-JLR200

Published

31-03-2021

How to Cite

Ali, R., Baban, R., & Ali, S. (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), 48–59. https://doi.org/10.47419/bjbabs.v2i01.38

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