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Oxidative modification of low-density lipoprotein in the artery wall plays a crucial role in the development of atherosclerosis. This physiopathological mechanism is clearly inhibited by high-density lipoprotein possibly via paraoxonase enzyme activity, present in high-density lipoprotein. In this study, we determined the in vitro susceptibility of low-density lipoprotein to oxidation and the effect of various factors, such as paraoxonase phenotypes, on this process. Low-density lipoprotein from healthy volunteers (n=66) was isolated using the precipitant reagent and the oxidation was evaluated by measuring the malonyl dialdehyde and diene levels. Low-density lipoprotein cholesterol and phospholipid, vitamin E, serum cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol levels, and erythrocyte antioxidant enzymes were also determined. There was no difference among the parameters with regard to gender. Low-density lipoprotein samples obtained from subjects with the AA allele were more prone to oxidation, as observed by their higher stimulated conjugated diene (P=0.041) and thiobarbituric acid-related substance (P=0.042) levels, than samples from subjects with AB or BB alleles. The subjects with the BB allele had higher superoxide dismutase (P=0.021) and catalase (insignificant increase) activities, while their conjugated diene (P=0.000) levels were lower. In conclusion, our results revealed that the high low-density lipoprotein oxidation is related to the high low-density lipoprotein cholesterol content and low phospholipid content. The present study demonstrated an increase in superoxide dismutase and catalase activities, as well as PON1 activities, in subjects with the BB allele. Since these enzymes all show activity against low-density lipoprotein oxidation, we propose that future investigations on atherosclerotic processes should address PON1 polymorphism as well as PON1 and other antioxidant enzymes.

Background: Previous studies suggest that elevated oxidative stress implicates poor glycemic control resulting in the development of diabetic complications. By evaluating the relationship between paraoxonase (PON) and antioxidant enzyme activities and glycemic control in diabetic patients with and without complications, we investigated whether there is a role of PON and/or antioxidant status in glycemic control., Methods: A total of 107 patients with type 2 diabetes mellitus (DM) was included in the study. Seventy-five patients had complications including microangiopathy, proliferative retinopathy, and/or nephropathy while 32 had no complications. The control group consisted of 29 age- and sex-matched healthy persons. Serum superoxide dismutase (SOD) and catalase activities were measured according to Sun and Goth, respectively. Basal and salt-stimulated paraoxonase activities and arylesterase activity were determined using the method of Eckerson et al., Results: There was an increase in the catalase activity and a decrease in the basal and salt-stimulated PON activity of patients when compared with controls, while no significant difference was observed in SOD activity. PON phenotypes had no effect on any parameter in patient and control groups. The ratio of catalase/SOD was 2.44 +/- 7.10 and 0.17 +/- 0.09 in diabetics and controls, respectively (p = 0.004); this was associated with an elevation in HbA1c levels. On the other hand, catalase/PON ratio was also enhanced in diabetic patients (2.8 +/- 5.2), showing a relationship with HbA1c levels compared to controls (0.29 +/- 0.3, p = 0.000)., Conclusions: The data of this study reveal that enhanced catalase/SOD and catalase /PON ratios that are correlated with HbA1c levels are observed in diabetic patients; thus, these ratios may be used as markers of poor glycemic control and as risk factors in the development of diabetic complications.

Objectives: Type 2 diabetes mellitus (DM) is well recognized as being associated with increased prevalence of hypertension. Experimental and epidemiologic studies have shown that oxygen-free radicals are elevated because antioxidant enzyme activities are altered both in uncontrolled essential hypertension and DM itself. Recently paraoxonase (PON) has been recognized as an antioxidant enzyme that hydrolyzes lipid peroxides. The aim of this study is to evaluate simultaneously PON activities and antioxidant status in hypertensive type 2 DM cases and to establish any possible relationship between these parameters and duration of hypertension or diabetes, hemoglobin (Hb) A1c levels, and lipid parameters., Design and Methods: Nineteen normotensive subjects with type 2 DM, 37 hypertensive (diastolic blood pressure 90 mm Hg or more) subjects with type 2 DM, and 25 normotensive control subjects with normal glucose tolerance were selected for this study. Superoxide dismutase (SOD), catalase, and basal-stimulated PON activities were measured by the methods of Sun et al.; Goth; and Eckerson, Wyte, and La Du, respectively; other lipid parameters were determined using an autoanalyzer., Results: Catalase activities of either hypertensive patients with type 2 DM or type 2 DM patients without complication were found to be higher than controls (p<0.01), although no significant difference in SOD and basal-stimulated PON activities was observed between these groups. A significant elevation in catalase activity (p = 0.004) of patients with high HbA1c levels (>7.0%) (n = 37) compared with patients with low HbA1c levels (<7.0%) (n = 19) was detected. There was also a positive correlation between the catalase activities and fasting glucose levels and HbA1c concentrations in hypertensive patients with type 2 DM (r = 0.4567, p<0.05 and r = 0.3686, p<0.05, respectively). An increase in catalase activity of patients with B and/or AB phenotype compared with patients with A phenotype was also noted., Conclusion: Poor glycemic control in diabetes is strongly associated with an increase in free radicals and consequent diabetic complications. Uncontrolled glucose metabolism may also be the cause of alterations in antioxidant enzymes. Among these, catalase correlates best with poor glycemic control. The current data reveal that B allele carriers of PON are more susceptible to oxidant stress.