RESUMO
Serum paraoxonase [PON[1]] is a high-density lipoprotein [HDL] associated esterase with a hypothesized role in the protection of low density lipoprotein [LDL] from oxidative stress perhaps by hydrolysing phospholipid - hydroperoxides. The present study was designed to determine the activity and phenotype distribution of serum PON[1] in patients with chronic renal failure [CRF], to elucidate the effect of regular hemodialysis on the activity of this enzyme, and hence to assess whether changes in PON[I] activity might contribute to the accelerated development of atherosclerosis. The study included 60 unrelated patients with CRF on conservative management and in need of dialysis. They were 48 males and 12 females with a mean age of 43.8 +/- 9.2 years, 22 of them had evidence of stable cardiovascular disease [CVD] and the remaining 38 had no evidence of clinical or subclinical CVD. Thirty, sex- and age-matched unrelated apparently healthy subjects served as controls. The enzyme activities were measured spectrophotometrically with paraoxon and phenylacetate as substrate for paraoxonase and arylesterase respectively with estimation of phenotype distribution. The serum PON[1] activities and phenotype distribution were determined in all subjects after inclusion in the study with another determination of serum PON[1] activity in all patients after 6 months of regular hemodialysis.Before dialysis, the serum PON[1] activity was significantly lower in CRF patients with CVD than in CRF patients without CVD [P < 0.01] and in CRF patients without CVD than in controls [P < 0.001].To assess whether the altered PON[1] activity was due to decrease in HDL or apolipoprotein A[1] [apo-A[1]] levels. The enzyme activity for the HDL [PON[1] / HDL ratio] and apo-A[1] concentrations [PON[1] / apo-A[1] ratio] were standardized.We found that both ratios were significantly lower in CRF patients than in controls [P < 0.001] and in CRF patients with CVD than in CRF patients without this disease [P < 0.01] After 6 months of regular hemodialysis, serum PON[1] activity was significantly decreased in CRF patients with and without CVD compared with before dialysis [P < 0.001, P < 0.05, respectively].It was found that PON[1] activity was trimodally distributed and no significant difference in phenotype distribution was found between the different studied groups. In conclusion, the reduced PON[1] activity in patients with CRF particularly those with CVD, either before or after 6 months of regular hemodialysis, may give rise to decreased HDL antioxidant capacity. LDL modification by lipid peroxidation might therefore be increased, contributing to the accelerated development of atherosclerosis. Interventions that preserve or enhance PON[1] activity have to be examined in future studies