Decreased paraoxonase 2 enzymatic activity in monocyte/macrophages cells. A comparative in vivo and in vitro study for diabetes.

AIM: To investigate peripheral blood monocytes/macrophages (Mo/Mᴓ) paraoxonase 2 (PON2) in diabetes and the factors modulating its activity. METHODS: One hundred and eighteen patients with newly diagnosed uncomplicated type 2 diabetes mellitus were compared regarding clinical, biochemical and oxidative stress parameters with 80 healthy subjects. The capacity of the peripheral blood mononuclear cells (PBMNC) to release pro-oxidants and to neutralise them was determined by measuring the respiratory burst (RB) and the intracellular antioxidant enzyme PON2. In vitro experiments were conducted on a differentiated monocytes cell line (dU937) that was exposed to serum deprivation followed by addition of isolated lipoproteins (VLDL or LDL). RESULTS: Paraoxonase 2 activity in Mo/Mᴓ was significantly lower in type 2 diabetes patients (0.042 ± 0.044 vs 0.165 ± 0.133U lactonase activity/mg protein in controls, p < .0005) and decreased in the obese in all groups. It was inversely correlated to parameters of adiposity (BMI and Waist Circumference), of glucose control (blood glucose, fructosamine and HbA1c) and insulin resistance (HOMA-IR). In multivariate regression models, 15-34% of the PON2 variance was explained by diabetes. The in vitro addition of VLDL normalised the RB of serum deprived dU937 cells, S- (to 82 ± 18% of the cells incubated with serum, S+) and PON2 activity (from 0.524 ± 0.061 in S - to 0.298 ± 0.048 U/mg protein). In contrast, when LDL was added, the RB remained lower (61 ± 12% of S+, p = .03) and PON2 higher (0.580 ± 0.030 U/mg protein, p = .003). CONCLUSIONS: The decrease in monocyte/macrophage PON2 enzymatic activity observed in type 2 diabetes cannot be totally explained by abdominal obesity and insulin resistance. The underlying molecular mechanisms need to be identified.

Venous versus arterial iron administration in haemodialysis. Influence on erythrocytes antioxidant parameters.

Introduction Intravenous iron administration in patients treated by haemodialysis for end stage renal disease can exacerbate oxidative stress by increasing the level of free redox active iron. A way to reduce the impact of iron on oxidative stress in haemodialysis patients may be the administration of iron through arterial extracorporeal circuit. Objective The aim of our study was to compare the influence of iron route of administration (venous versus arterial extracorporeal circuit infusion) on antioxidant parameters in red blood cells of haemodialysis patients in order to clarify if arterial iron administration can have positive impacts related to iron induced oxidative stress. Method Twenty stable patients on regular haemodialysis treatment were selected for the study. They were investigated in a cross-over design at 3 mid-week HD sessions, one week apart, without iron [HD basal] and with either IV infusion of 100mg iron sucrose over the first 20 minutes of HD session, via venous line [HDvenous], or the same solution infused on the arterial extracorporeal circulation [HDarterial]. Blood samples were drawn at 0 min, 40 min and 270 min. Erythrocytes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activity, non-protein thiol levels and total antioxidant capacity (TEAC) were analysed. Conclusion Haemodialysis significantly decreases the total antioxidant activity in erythrocytes. Iron supplementation, through venous or arterial extracorporeal route has no impact on the total antioxidant activity in red blood cells. Venous iron administration increases GPx activity in erythrocytes suggesting increased lipid peroxidation compared with arterial extracorporeal administration.