leukotriene-b4 and Renal-Insufficiency--Chronic

Neutrophils release leukotriene (LT)B. This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD.. In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks.. Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB. n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB

Topics: Adult; Aged; Dietary Supplements; Double-Blind Method; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Humans; Hydroxyeicosatetraenoic Acids; Inflammation Mediators; Leukotriene B4; Male; Middle Aged; Neutrophils; Peroxidase; Renal Insufficiency, Chronic; Ubiquinone

The proinflammatory leukotriene B₄ (LTB₄) may be of importance in the progression of chronic kidney disease (CKD). We investigated whether n-3 polyunsaturated fatty acids (PUFA) decrease LTB₄ and increase the formation of the less inflammatory leukotriene B₅ (LTB₅) in patients with CKD. Fifty-six patients with CKD stage 2-5 were randomised to 2.4 g n-3 PUFA or olive oil for 8 weeks. Compared to controls, n-3 PUFA significantly decreased release of LTB₄ (p<0.001) and 5-hydroxyeicosatetraenoic acid (5-HETE) (p<0.01) and significantly increased release of LTB₅ (p<0.001) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p<0.001) from stimulated neutrophil granulocytes. Kidney function evaluated by creatinine clearance and proteinuria did not improve. In conclusion, n-3 PUFA supplementation for 8 weeks in patients with CKD stage 2-5 significantly decreased LTB₄ and 5-HETE and significantly increased LTB₅ and 5-HEPE. No effect was seen on kidney function.

Topics: Dietary Supplements; Double-Blind Method; Down-Regulation; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Female; Fish Oils; Granulocytes; Humans; Kidney; Leukotriene B4; Male; Middle Aged; Neutrophil Activation; Neutrophils; Patient Dropouts; Renal Insufficiency, Chronic; Severity of Illness Index; Up-Regulation

The role of vitamin E in both enzymatic and free radical-dependent metabolism of polyunsaturated fatty acids (PUFAs) has been well demonstrated. This study proposed a new LC-MS/MS method to quantify the main vitamin E forms, their metabolites and main PUFA species in human blood, since, at present, there are not procedures able to simultaneously determine these two classes of compounds. After the optimization of sample treatment and reverse-phase separation conditions, tandem mass spectrometry detection was evaluated experimenting both positive and negative electrospray ionisation modes. The procedure was also preliminarily adapted to assess five arachidonic acid-derived eicosanoids that could be under the influence of vitamin E function, such as LTB4 (leukotriene B4), 20-HETE (20-hydroxyeicosatetraenoic acid) and their ω-oxidation metabolites. After the validation study, the performance characteristics were confirmed analysing a certified reference material (SRM

Topics: Adult; Arachidonic Acid; Case-Control Studies; Chromatography, Liquid; Eicosanoids; Fatty Acids, Unsaturated; Female; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Male; Middle Aged; Renal Insufficiency, Chronic; Tandem Mass Spectrometry; Vitamin E