Serum paraoxonase activity and oxidative stress in patients with adult nephrotic syndrome (original) (raw)
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Journal of Nephropathology
Increased reactive oxygen species (ROS) in nephrotic syndrome (NS) are involved in the oxidation of membrane proteins, lipoproteins and several receptor molecules ultimately leading to their functional deficit. It is involved in the pathogenesis of dyslipidemia in NS and also increases the oxidation of LDL (oxLDL), which is an important risk factor in thrombus generation and atherosclerosis. Myeloperoxidase (MPO) is an early predictor of myocardial infarction and adverse cardiac events in patients with chest pain. MPO can also foresee the recurrent acute coronary syndrome (ACS) and myocardial infarction in patients. ‘MPO oxidized LDL’ also induces ROS production, lipid accumulation and reduces the antioxidant response in macrophages, however in an augmented way by using different pathways and might be more atherogenic. Paraoxonase 1 (PON1) prevents the oxidative modification of serum lipoproteins, which is one of the crucial steps in the initiation of atherogenesis. PON1 also contri...
PARAOXONASE 1 AND CARDIOVASCULAR RISK IN NEPHROTIC SYNDROME PATIENTS
TJPRC, 2014
Background: Abnormal lipoprotein metabolism is a common characteristic of nephrotic syndrome. But this dyslipidemia cannot fully explain the increased incidence of atherosclerosis in this population. HDL associated enzyme, paraoxonase 1 (PON1), prevents the formation of oxidized LDL, which is an important culprit in the development of cardiovascular disease and therefore reduced PON1 is found to be an independent risk factor for atherosclerosis. Objective: The primary intention of this study is to analyze the PON1 levels in nephrotic syndrome along with lipid profile and atherogenic index, thus trying to provide a clearer picture of cardiovascular risk in nephrotic syndrome patients. Method: 40 newly diagnosed nephrotic syndrome patients were included in the study. Equal number of age and sex matched healthy controls were also selected. Basal and salt stimulated activity of PON1 was measured along with lipid profile and atherogenic index. Results: There was a significant decrease of PON1 activity in nephrotic syndrome patientscompared to the healthy controls. Total cholesterol, LDL, triglycerides, VLDLand Atherogenic Index were high and HDL cholesterol level was low in nephrotic syndrome patients. Moreover a significant negative correlation was observed between PON1 and Atherogenic index and a positive correlation between PON1 and HDL-cholesterol in both cases and controls. Conclusions: Therefore the study reveals an increased risk of cardiovascular disease in nephrotic syndrome patients. Hence measuring PON1and Atherogenic index during the initial stages of nephrotic syndrome mayhelp in predicting the extent of the associated cardiovascular risk.
Paraoxonase‐1 (PON1) activity as a risk factor for atherosclerosis in chronic renal failure patients
Hemodialysis …, 2008
Paraoxonase is a high-density lipoprotein-associated enzyme and has been shown to reduce the susceptibility to low-density lipoprotein peroxidation. This study aimed to investigate the activity of serum paraoxonase in uremic patients on hemodialysis (HD) and in the predialysis period, and to evaluate the correlations of vascular disease with paraoxonase activity. Thirty patients with chronic renal failure (CRF) undergoing HD (group 1), 30 patients with CRF under conservative treatment (group 2), and 30 healthy controls (group 3) were included. Basal, salt-stimulated, and arylesterase activity were tested by UV spectrophotometry. Serum lipid parameters were determined. B-Mode Doppler ultrasound was used to assess common carotid intima-media thickness (IMT). Basal paraoxonase, salt-stimulated, and arylesterase activity showed no significant difference between group 1 and group 2. However, it was significantly lower in group 1 and in group 2 than controls. Carotid IMT was significantly higher in group 1 than group 2 and both were significantly higher than controls. Basal paraoxonase-1 (PON1), salt-stimulated PON1, and arylesterase activity correlate with BUN, but only basal PON1 and salt-stimulated PON1 correlate with serum albumin. Linear regression showed that the most significant determinant of carotid IMT was PON1 arylesterase activity in group 1 and arylesterase activity and basal PON1 activity in group 2. Patients with CRF, whether under HD or conservative treatment, have reduced basal and stimulated paraoxonase activities, and this could be an important factor causing increased vascular disease in those patients. Modifying this factor can be of great value to protect against this common complication.
PON1 status is influenced by oxidative stress and inflammation in coronary heart disease patients
Clinical Biochemistry, 2008
High-density lipoprotein (HDL) associated paraoxonase 1 (PON1) is an essential component of HDLs' capability to protect low-density lipoproteins (LDL) from oxidative modification and thus to limit the atherosclerotic process. The aim of the current study was to investigate the association between oxidative stress status, indices of inflammation and PON1 status parameters.We determined the relationship between the oxidative stress status, inflammatory markers and PON1 status parameters in 261 middle-aged subjects: 156 coronary heart disease (CHD) patients and 105 CHD-free subjects (as the control group). The PON1 status involved PON1 activity measurements towards two substrates: paraoxon (POase activity) and diazoxon (DZOase activity) and subsequent PON1Q192R activity phenotype determination.A statistically significant greater malondialdehyde (MDA) concentration in the RR phenotype subjects compared to QQ subjects within the CHD group was apparent (P < 0.05). Multiple linear regression analysis revealed an independent influence of plasmatic SOD activity (P < 0.05) on POase values and MDA (P < 0.01) and O2Our CHD patients were in a state of oxidative stress, which was most evident in the RR phenotype group. The QQ phenotype group is associated with the lowest oxidative stress status level and also with a better capacity for anti-oxidative protection. Oxidative stress in CHD patients is maintained by systemic low-grade inflammation, which results in PON1 enzymatic activity exhaustion. Therefore, deeper investigation of an effective anti-oxidative and anti-inflammatory therapy should be necessary in order to increase anti-oxidative potency and improve PON1 status of CHD patients.
Oxidative Stress & Antioxidants and PON1 in Health and Disease
The Paraoxonases: Their …, 2008
Impairment in oxidative stress/antioxidant balance is an important trigger for a variety of diseases. As an antioxidant molecule on HDL, paraoxonase (PON) contributes to the antioxidant mechanisms by removing oxidised lipids both on HDL and LDL. In this chapter, we will document and evaluate the results of our studies on healthy, atheroscleoric and diabetic cases which showed that (a) PON, superoxide dismutase (SOD) and arylesterase probably work in a collaboration against oxidative stress, especially superoxide radical scavenging; (b) PON and SOD activities concomitantly decrease with the oxidative stress & severity of disease (higher HbA1c values in diabetics, more diseased vessels in atherosclerosis) while catalase (CAT) acts the opposite way; (c) depletion of PON activity may be mainly attributed to oxidative inactivation by lipid hydroperoxides; (d) Since PON1 activity and eTBARS levels are affected by traditional risk factors (hypertension, aging and gender), determination of arylesterase activity might be a better indicator of antioxidant activity of PON1; (e) SOD activity has the greatest variability in EY SOZMEN ET AL regard to PON phenotype therefore it's important to define the PON1 polymorphism as well as PON, arylesterase and other antioxidant enzyme activities. Enhancement of free radicals and impairment of antioxidant status are crucial processes underlying pathophysiologic mechanisms in a variety of diseases including atherosclerosis, diabetes mellitus and cancer (Mates JM, Parthasarathy S, Aguirre F). Enzymatic and nonenzymatic antioxidant systems (such as superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase-GPx, paraoxonase-PON and vitamin E) are important in scavenging free radicals and their metabolic products as well as in maintaining normal cellular physiology, promotion of immunity and prevention of various diseases (Mates JM). Experimental, clinical and epidemiological studies have shown the depletion of various antioxidants in a variety of diseases (Mates JM, Parthasarathy S, Aguirre F, Maxwell SRJ). In this review, we focused on oxidative stress and antioxidant systems both in healthy humans and in patients with atherosclerosis and diabetes, emphasizing the changes in oxidant/antioxidant status in regard to PON phenotyping as well as PON genotyping in order to elucidate the antioxidant role of PON. Relationship between PON and other antioxidant enzymes in healthy humans and in diseases According to the "oxidative modification hypothesis", atherogenesis is initiated by oxidation of the low-density lipoprotein (LDL) (Ross R, Aviram M 1996, Steinberg D, Chisolm GM) and increasing evidence suggests that this modification plays a central role in the further propagation of atherogenesis as well (Jialal I, Chisolm GM, Kaplan M, Steinberg D, Parthasarathy S). The LDL oxidative state is elevated by increased ratio of poly/mono unsaturated fatty acids in LDL and it is reduced by enhanced LDL-associated antioxidant content such as vitamin E, beta-carotene, EY SOZMEN ET AL lycopene, polyphenolic flavonoids and other external antioxidants (Aviram M 2005). Recently it has been shown that PON1 prevents LDL from oxidation by removing oxidised phosholipids from LDL. This is supported by the finding in PON1-knock out mice in which PON's preventive effect on LDL oxidation was not observed (Mackness MI 1996, Laplaud RM, Durrington PN, Shih DM). Apart from PON, other antioxidant systems are important in the prevention of various diseases by scavenging free radicals (Mates JM). Previous research on PON and antioxidants (such as SOD, CAT, GPx, etc.) triggered our work on the role of antioxidant enzymes in the maintenance of PON activity during LDL oxidation in various groups namely, healthy, diabetic and atherosclerotic cases. Our first study indicated a negative correlation between PON activities and conjugated diene (r= -0.297, p=0.034) & TBARS (r= -0.265, p=0.053) levels of LDL at baseline (Sozmen EY, 2001b). Another important finding of our study was the positive correlation between SOD and PON activity in healthy cases (n=66) (Figure-1).
International Journal of Cardiology, 2003
Background: There is growing evidence that ox-LDL plays an important role during the atherosclerosis process and PON1 can significantly inhibit generation of lipid peroxidation during LDL oxidation and thus play a role in the in vivo protection by HDL against atherosclerosis. Methods: Twenty-four healthy volunteers and one-hundred and one patients were taken into study, sixty-eight patients had coronary artery disease which was confirmed by coronary angiography. Serum PON1, erythrocyte superoxide dismutase and catalase activities, oxidative markers of LDL were determined along with the routine biochemical parameters in all groups. Results: The indicators of oxidative stress were higher in the patients compared with the controls. No statistically significant difference in any of parameters were observed between the patients who had obstruction with different degrees except for erythrocyte TBARS [24.5 nmol / g Hb in patients with one vessel disease (VD) (n522), 29.6 nmol / g Hb in patients with two VD (n526) and 33.5 nmol / g Hb in patients with three VD (n520)]. Basal and stimulated diene levels were higher in patients who had more diseased vessels than those who had less. Conclusion: The increase in erythrocyte TBARS and CRP levels with the severity of disease supports the reports that showed the inflammatory and oxidative nature of atherosclerosis. In the light of the fact that the well-known classical risk factors for atherosclerosis are closely associated with increased oxidative stress, we propose that the elevation in TBARS levels might be a more marked indicator for the degree of atherosclerosis than the insufficiency in antioxidant enzymes such as SOD and PON1.
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, 2018
Hypertension is a trait opposed to a specific disease and with an ongoing global increase in the incidence. Hypertension is classified into two groups, primary or essential hypertension, and secondary hypertension. Primary hypertension is defined as a rise in blood pressure of unknown cause and secondary is caused by disease of kidney, endocrines or some other organs. An individual with hypertension is at increased risk factor for stroke, heart disease, and kidney failure [1]. Oxidative stress is defined when there is an imbalance between the reactive oxygen species generation and the antioxidant defence system. Increased vascular oxidative stress could be involved in the pathogenesis of hypertension. Lipid peroxidation is a chain reaction initiated by free radicals which provides a continuous supply of other free radicals formed from unsaturated fatty acids which further initiate peroxidation. Malondialdehyde, the end product of lipid per-oxidation can be used as a marker for lipid peroxidation and oxidative stress. Paraoxonase 1 (PON1), an enzyme which is found exclusively associated with HDL in serum. It protects LDL from oxidation. In humans, PON 1 is an independent, genetic risk factor for coronary artery disease [2,3] and low PON1 activities are observed in atherosclerotic and hypercholesterolemic patients [2,4-6]. An important role is played by PON 1 in the antioxidant system as it is thought to degrade oxidised phospholipids in lipoproteins [7]. In the diseases involving oxidative stress, the circulating PON 1 levels have been found to be altered [8].
Kidney International, 2005
Increased phagocytic nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production in patients with early chronic kidney disease. Background. Oxidative stress has been implicated in the pathogenesis of atherosclerosis that develops in patients with advanced chronic kidney disease (CKD). This study was designed to investigate whether a relationship exists between phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide anion (•O 2 −) production and subclinical atherosclerosis in patients with early CKD. Methods. Superoxide production was assayed by chemiluminescence under baseline and stimulated conditions on mononuclear cells obtained from asymptomatic patients with stage 1 to 2 CKD (N = 22) and healthy controls (N = 21). Ultrasonographic determination of carotid intima-media thickness (IMT) was used to assess the presence of atherosclerosis. Results. Although there were no differences in baseline •O 2 − production between controls and patients, the •O 2 − production in phorbol myristate acetate-stimulated mononuclear cells was increased (P < 0.05) in patients compared with controls. The phorbol myristate acetate-induced •O 2 − production was completely abolished by apocynin, a specific inhibitor of NADPH oxidase. A direct correlation (r = 0.441, P < 0.05) was found between plasma insulin levels and NADPH oxidase-mediated •O 2 − production in patients. Carotid IMT was higher (P < 0.005) in patients than in controls. Carotid IMT values above the upper normal limit in controls were found in 70% and 40% of patients with increased or normal NADPH oxidase-mediated •O 2 − production, respectively. Conclusion. Generation of •O 2 − that is mainly dependent on NADPH oxidase is abnormally enhanced in patients with early CKD. It is suggested that this alteration could be related to the development of subclinical atherosclerosis in these patients. Patients with stage 3 to 5 chronic kidney disease (CKD), according to the National Kidney Foundation
Phenotypes and concentration of PON1 in cardiovascular disease: the role of nutrient intake
Nutrition, Metabolism and Cardiovascular Diseases, 2019
Background and aims: Paraoxonase 1 (PON1) is considered to play a crucial role as an anti-atherosclerotic factor. The PON1 activity is affected by genetic polymorphisms, environmental factors, age, sex, lifestyle, pharmaceutical drugs, and dietary factors. The aim of this study was to evaluate the association between macro-and micronutrients as well as PON1 concentration and activities in patients with cardiovascular diseases (CVD), cardiovascular risk factors but no CVD (CRF), and in healthy controls (control group). Methods and results: A case-control study was carried out with 356 volunteers from the Mexican Institute of Social Security, Mexico. Clinical parameters, lipid profile, PON1 activities (AREase, LA-Case, CMPAase and PONase), and PON1 concentration were evaluated. There was a differential intake of macro-and micronutrients among the study groups. The intake of proteins and carbohydrates was higher in the CVD group than in the CFR and control groups (p < 0.05). AREase, LACase, and CMPAase activities and PON1 concentration were lowest in the CVD group. Conclusion: LACase and CMPAase activities, as well as PON1 concentration, could be included in the battery of CVD predictive biomarkers in the Mexican population.