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Paraoxonase-1 activity in type 2 diabetes mellitus with and without nephropathy
The Egyptian Journal of Internal Medicine volume 27, pages 63–68 (2015)
Abstract
Background
Paraoxonase-1 (PON-1) is an enzyme synthesized in the liver that has antioxidant functions as it binds to the HDL particles and prevents the oxidation of LDL, which possibly plays a role in the prevention of atherosclerosis and coronary artery disease.
Objectives
To determine PON-1 activity in type 2 diabetic patients with and without diabetic nephropathy and its correlation with the lipid profile, disease duration, and glycemic status.
Patients and methods
This study was carried out on 30 patients with type 2 diabetes mellitus who attended the diabetes and endocrine clinic at Kasr Al Ainy Hospital, Cairo University, including 20 patients with evidence of diabetic nephropathy and 10 patients without diabetic nephropathy as well as 15 healthy age-matched control participants. Fasting blood sugar, 2 h postprandial blood sugar, total cholesterol, HDL, LDL, triglycerides, and serum creatinine were measured. PON-1 activity was detected using a colorimetric method.
Results
PON-1 activity was reduced significantly in diabetic patients with and without nephropathy, with mean 226.1 ± 135.4 and 221.7 ± 119.6 nmol/ml/min, respectively, versus 758.5 ± 353.9 nmol/ ml/min in the control group (P < 0.001). PON-1 activity was not significantly different between diabetic patients with and without nephropathy. PON-1 activity was correlated negatively with HDL (r = −0.496, P = 0.026) in diabetic patients with nephropathy. PON-1 activity was not correlated significantly with disease duration and glycemic status.
Conclusion
PON-1 activity was significantly reduced in type 2 diabetes, but did not differ between diabetics with or without nephropathy.
References
American diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2009; 32:S26–S67.
Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes 1991; 40:405–412.
Dihazi H, Müller GA, Lindner S, Meyer M, Asif AR, Oellerich M, Strutz F. Characterization of diabetic nephropathy by urinary proteomic analysis: identification of a processed ubiquitin form as a differentially excreted protein in diabetic nephropathy patients. Clin Chem 2007; 53:1636–1645.
Prabhakar S, Starnes J, Shi S, Lonis B, Tran R. Diabetic nephropathy is associated with oxidative stress and decreased renal nitric oxide production. J Am Soc Nephrol 2007; 18:2945–2952.
Ha H, Kim KH. Pathogenesis of diabetic nephropathy: the role of oxidative stress and protein kinase C. Diabetes Res Clin Pract 1999; 45:147–151.
Li HL, Liu DP, Liang CC. Paraoxonase gene polymorphisms, oxidative stress, and diseases. J Mol Med (Berl) 2003; 81:766–779.
Rani JA, Mythili SV. Paraoxonase 1 in type 2 diabetes mellitus – a review. Int J Pharm Sci Rev Res 2014; 28:175–179.
Costa LG, Cole TB, Jarvik GP, Furlong CE. Functional genomic of the paraoxonase (PON1) polymorphisms: effects on pesticide sensitivity, cardiovascular disease, and drug metabolism. Annu Rev Med 2003; 54:371–392.
Mackness B, Davies GK, Turkie W, Lee E, Roberts DH, Hill E, et al. Paraoxonase status in coronary heart disease: are activity and concentration more important than genotype?. Arterioscler Thromb Vasc Biol 2001; 21:1451–1457.
Seres I, Paragh G, Deschene E, Fulop T Jr, Khalil A. Study of factors influencing the decreased HDL associated PON1 activity with aging. Exp Gerontol 2004; 39:59–66.
Jenkins AJ, Best JD, Klein RL, Lyons TJ. Lipoproteins, glycoxidation and diabetic angiopathy. Diabetes Metab Res Rev 2004; 20:349–368
World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications, 1999
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499–502.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39(Suppl 1): S1–S266.
Sampson MJ, Braschi S, Willis G, Astley SB. Paraoxonase-1 (PON1) genotype and activity and in vivo oxidized plasma low-density lipoprotein in type II diabetes. Clin Sci (Lond) 2005; 109:189–189.
Abbott CA, Mackness MI, Kumar S, Boulton AJ, Durrington PN. Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. Arterioscler Thromb Vasc Biol 1995; 15:1812–1818.
Mackness B, Durrington PN, Abuashia B, Boulton AJ, Mackness MI. Low paraoxonase activity in type II diabetes mellitus complicated by retinopathy. Clin Sci (Lond) 2000; 98:355–363.
Karabina SA, Lehner AN, Frank E, Parthasarathy S, Santanam N. Oxidative inactivation of paraoxonase – implications in diabetes mellitus and atherosclerosis. Biochim Biophys Acta 2005; 1725:213–221.
Valabhji J, McColl AJ, Schachter M, Dhanjil S, Richmond W, Elkeles RS. High-density lipoprotein composition and paraoxonase activity in type I diabetes. Clin Sci (Lond) 2001; 101:659–670.
Kopprasch S, Pietzsch J, Kuhlisch E, Graessler J. Lack of association between serum paraoxonase 1 activities and increased oxidized low-density lipoprotein levels in impaired glucose tolerance and newly diagnosed diabetes mellitus. J Clin Endocrinol Metab 2003; 88: 1711–1716.
Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med 2000; 28:1708–1716.
Ferretti G, Bacchetti T, Marchionni C, Caldarelli L, Curatola G. Effect of glycation of high density lipoproteins on their physicochemical properties and on paraoxonase activity. Acta Diabetol 2001; 38:163–169.
Hedrick CC, Thorpe SR, Fu MX, Harper CM, Yoo J, Kim SM, et al. Glycation impairs high-density lipoprotein function. Diabetologia 2000; 43:312–320.
Deakin S, Leviev I, Gomaraschi M, Calabresi L, Franceschini G, James RW. Enzymatically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem 2002; 277:4301–4308.
Ikeda Y, Suehiro T, Inoue M, Nakauchi Y, Morita T, Arii K, et al. Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus. Metabolism 1998; 47:598–602.
Khodeir SA, Abd El Raouf YM, Amer AE, El Fadaly NH, Abd El Latif EA. Paraoxonase gene polymorphism and activity in type 2 diabetes mellitus with microvascular complications. J Am Sci 2012; 8:27–34.
Vanitha Gowda MN, Kusuma KS, Vasudha KC. Serum paraoxonase (Arylesterase) activity in type 2 diabetes mellitus and diabetic nephropathy. Indian J Appl Res 2013; 3:351–353.
Elattar N, Swelam EE, Hamed E, Elnahal A, Mostafa E. Paraoxonase 1 gene polymorphism relationship with type 2 diabetes mellitus. Life Sci J 2012; 9:1742–1751.
Kordonouri O, James RW, Bennetts B, Chan A, Kao YL, Danne T, et al. Modulation by blood glucose levels of activity and concentration of paraoxonase in young patients with type 1 diabetes mellitus. Metabolism 2001; 50:657–660.
Saha N, Roy AC, Teo SH, Tay JS, Ratnam SS. Influence of serum paraoxonase polymorphism on serum lipids and apolipoproteins. Clin Genet 1991; 40:277–282.
Deepthi SK, G, Amar Raghu Narayan. Paraoxonase activity and its concentration in type 2 diabetes mellitus. Int J Pharm Bio Sci 2012; 3:969–973.
Patil Asmita B, Ganu Jayashree V. Paraoxonase 1, total cholesterol and HDL cholesterol in diabetes mellitus. Indian J Basic Appl Med Res 2013; 2:998–1001.
Tomas M, Latorre G, Senti M, Marrugat J. The antioxidant function of high density lipoproteins: a new paradigm in atherosclerosis. Rev Esp Cardiol 2004; 57:557–569.
Kural BV, Orem C, Uydu HA, Alver A, Orem A. The effects of lipid-lowering therapy on paraoxonase activities and their relationships with the oxidant-antioxidant system in patients with dyslipidemia. Coron Artery Dis 2004; 15:277–283.
Hegele RA, Brunt JH, Connelly PW. A polymorphism of the paraoxonase gene associated with variation in plasma lipoproteins in a genetic isolate. Arterioscler Thromb Vasc Biol 1995; 15:89–95.
Mackness B, Durrington PN, Boulton AJ, Hine D, Mackness MI. Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controls. Eur J Clin Invest 2002; 32:259–264.
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El-said, N.H., Nasr-Allah, M.M., Sadik, N.A. et al. Paraoxonase-1 activity in type 2 diabetes mellitus with and without nephropathy. Egypt J Intern Med 27, 63–68 (2015). https://doi.org/10.4103/1110-7782.159451
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DOI: https://doi.org/10.4103/1110-7782.159451