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Protective Effect of Paraoxonase Activity in High-Density Lipoproteins against Erythrocyte Membranes Peroxidation: A Comparison between Healthy Subjects and Type 1 Diabetic Patients

Istituto di Biochimica (G.F., T.B., G.C.), Università Politecnica delle Marche, 60131 Ancona, Italy; Unità Operativa di Dietetica e Nutrizione Clinica (D.B.), Azienda Ospedaliera Umberto I, 60020 Ancona, Italy; and Unità Operativa di Diabetologia (R.A.B.), Istituto Nazionale di Riposo e Cura per Anziani, 60131 Ancona, Italy

Address all correspondence and requests for reprints to: Dott. Tiziana Bacchetti Istituto di Biochimica, Facoltà di Medicina Università Politecnica delle Marche via Ranieri 67 I-60131, Ancona, Italy. E-mail: tbacchet{at}tiscalinet.it.

High-density lipoproteins (HDL) plays a key role in the protection against oxidative damage of lipoprotein and biological membranes. The aim of the present study was to investigate the relationship between the antioxidant role of HDL and the HDL-paraoxonase (PON) activity in healthy subjects and in type 1 diabetic patients. Moreover, the ability of HDL of controls and diabetic patients to protect and/or repair biological membranes from oxidative damage was studied.

HDL were isolated from 31 type 1 diabetic patients and 31 sex- and age-matched healthy subjects and immediately used to evaluate lipid hydroperoxides and HDL-PON activity. Erythrocyte membranes obtained from healthy subjects were oxidized with 2,2-azo-bis(2-aminidinopropane)dihydrochloride and then incubated in the presence of HDL isolated from healthy or type 1 diabetic subjects, with measurements of membrane lipid hydroperoxides before and after the incubation. HDL from type 1 diabetic patients showed higher levels of lipid hydroperoxides and a lower activity of HDL-PON than healthy subjects. Moreover, HDL of type 1 diabetic patients protected less efficiently erythrocyte membranes against oxidative damage compared with HDL from healthy subjects. A negative correlation was found between HDL-PON activity and the levels of hydroperoxides of HDL, confirming the relationship between PON and lipid peroxidation and suggesting that subjects with low PON activity are more exposed to oxidative damage than subjects with high PON activity.

The ability of HDL to protect erythrocyte membranes was positively correlated with HDL-PON activity and negatively correlated with the levels of lipid hydroperoxides of HDL of healthy subjects. These results confirm a linkage between PON activity and lipid peroxidation of lipoproteins and suggest that the ability of HDL to protect erythrocyte membranes might be related to the PON activity.

It might be hypothesized that the decrease of PON activity in diabetic patients and the lower HDL protective action against membrane peroxidation could contribute to acceleration of arteriosclerosis in type 1 diabetes mellitus.

Abbreviations: AAPH, 2,2-Azo-bis(2-aminidinopropane)dihydrochloride; HbA_1c, glycated hemoglobin A1c; HDL, high-density lipoprotein(s); LCAT, lecithin:cholesterol acyltransferase; LDL, low-density lipoprotein(s); ns, not significant; PON, paraoxonase.

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