Serum paraoxonase 1 (PON1) lactonase activity is lower in end-stage renal disease patients than in healthy control subjects and increases after hemodialysis
-
Alejandro Gugliucci
,
Eriko Kinugasa
Abstract
Background: The mechanism of paraoxonase 1 (PON1) atheroprotective remains elusive. The lactonizing/lactonase activity of PON1 is gaining favor as the most significant in physiology.
Methods: We studied 42 end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) and 49 control subjects. We measured PON1 lactonase, arylesterase and triesterase activities by kinetic methods.
Results: Serum lactonase activity was 11% lower in ESRD patients (p<0.0001) and did not correlate with high-density lipoprotein (HDL) cholesterol when controlling for confounders. Lactonase activity was significantly higher after dialysis. Using a repeated measure-ANOVA adjusted for the confounders (age, gender, total cholesterol, triglyceride and HDL cholesterol) we show that the changes in lactonase after dialysis were significant (p<0.0001). HD increases lactonase activity to levels indistinguishable from those of control subjects. In simple linear regression analyses we showed a significant inverse correlation between changes in lactonase and those of creatinine by dialysis (r=–0.339, p=0.028).
Conclusions: ESRD patients maybe more susceptible to lipid peroxidation and to protein homocysteinylation than healthy subjects due to the decreased activity of lactonase. A lower serum lactonase activity would be coupled with delayed catabolism of oxidized phospholipids in low-density lipoprotein and oxidized macrophages, and with greater protein homocysteinylation, accelerating atherogenesis. One mechanism for lower lactonase activity in ESRD patients may be inhibition by uremic toxins and oxidative stress. The pathophysiology of reduced lactonase activity in uremia and the beneficial effects of HD need further investigation.
©2011 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Publisher's Note
- Publisher's Note
- Editorials
- Full-Disclosure in Industry-Sponsored Laboratory Medicine Research Studies: Statement by the Consortium of Laboratory Medicine Journal Editors
- Association of malignant mesothelioma and asbestos related conditions with ovarian cancer: shared biomarkers and a possible etiological link?
- Pharmacogenomics of alcohol metabolism: implications for legal testing
- Reviews
- Non-invasive assessment of liver fibrosis: it is time for laboratory medicine
- Application of proteomics to prenatal screening and diagnosis for aneuploidies
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