Roles of Paraoxonase and Oxidative Stress in Adolescents with Uraemic, Essential or Obesity-Induced Hypertension

Abstract

Background/Aims: Paraoxonase 1 (PON1) is associated with high-density lipoproteins in the plasma, and is capable of hydrolysing oxidized lipids and preventing the oxidation of low-density lipoproteins. Oxidative stress and the PON1 (activity and Q192R polymorphism) were analysed in adolescent patients with essential (n = 49) or obesity-induced hypertension (n = 79), uraemic patients (n = 20), and also in obese normotensive patients (n = 60) and age-matched controls (n = 57). Methods: The PON1 activity was measured via paraoxon hydrolysis. The PON1 genotype was determined by real-time PCR. The levels of oxidized and reduced glutathione, the end-products of nitric oxide, cysteine, homocysteine and lipid peroxidation in the plasma were measured and related to the PON1 status. Results: There were no significant differences between the patient groups and the control group in the genotype distributions and the allele frequencies of the Q192R polymorphism. The PON activity was significantly lower (p < 0.001) in the uraemic hypertensive group than in the controls. The MDA concentration was significantly higher in the uraemic hypertensive (p < 0.001) and obese hypertensive (p < 0.05) patients. The plasma NO_x concentrations were significantly lower (p < 0.001) and the ratio MDA/NO_x were significantly higher in all four patient groups. The GSH levels were significantly lower in the patients with hypertension (p < 0.001) and obesity-induced hypertension (p < 0.05) than in the controls, while the GSSG level (p < 0.01) and the ratio GSSG/GSH (p < 0.05) was significantly higher in the uraemic hypertensive group. The plasma homocysteine level was significantly higher (p < 0.001) in the uraemic hypertensive patients as compared with the controls. Conclusions: We found no significant correlation between the biochemical parameters and neither genotypes nor enzyme activities. The PON1 status and the levels of certain biochemical parameters are independently associated with the hypertension in hypertensive and obese hypertensive patients, and the elevated levels of lipid peroxides and plasma homocysteine may contribute to the increased risk of cardiovascular complications in patients on haemodialysis.

Genetics of Oxidative Stress in Obesity

“…A study conducted in Portuguese women showed an association of the R allele with a higher risk of obesity [26], whereas a study in Mexican adults revealed no association between the variant and risk of obesity [25]. Another study failed to find any association of the SNP with obesity in adolescents [68]. Our group recently published a study carried out in prepubertal children that also confirmed the lack of an effect of Q192R on childhood obesity risk [37].…”

Lipid Peroxidation, Nitric Oxide Metabolites, and Their Ratio in a Group of Subjects with Metabolic Syndrome

“…In this reexamination of our group of MS subjects, we calculated also the TBARS/NO x ratio that, up to now, has been evaluated in preeclampsia [29], in juvenile essential hypertension [30], and in hypertensive adolescents with obesity or uraemia [31, 32]. In MS the TBARS/NO x ratio may be considered as an integrated marker of plasma lipid peroxidation and degree of inflammation.…”

Assessment of microvascular reactivity and oxidative stress in hypertensive adolescents and hemodialysis patients

“…In line with this, increased levels of oxidized glutathione (GSSG), elevated ratios of oxidized/reduced glutathione (GSSG/GSH), decreased GSH levels, impaired GSH regeneration and a more pronounced lipid peroxidation have been demonstrated in adolescent hypertensives [43]. However, no differences were observed in the paraoxonase-1 (PON1) activities, PON1 Q192R genotype or homocysteine levels in this patient group, irrespective of the degree of obesity [44]. Next, we set out to examine whether a short-term antihypertensive treatment could reveal differences in markers of oxidative stress and endothelial dysfunction between lean or obese hypertensive adolescents [45].…”