losartan-potassium and 4-hydroxy-2-nonenal

Patients with end-stage renal failure undergoing haemodialysis (HD) are exposed to oxidative stress. Increased levels of malondialdehyde (MDA) were demonstrated in plasma of uraemic patients, indicating accelerated lipid peroxidation (LPO) as a consequence of multiple pathogenetic factors. The aim of our investigation was to examine the role of renal anaemia in oxidative stress in HD patients.. MDA and 4-hydroxynonenal (HNE) were measured in three groups of patients undergoing HD: group I comprised eight patients with a blood haemoglobin (Hb) < 10 g/dl (mean Hb = 8.1+/-1.3 g/dl), and group II were eight patients with a Hb > 10 g/dl (mean Hb=12.4+/-1.9g/dl); none of these 16 patients had been treated with human recombinant erythropoietin (rHuEpo). Group III comprised 27 patients with a mean Hb of 10.5+/-1.6 g/dl after long-term rHuEpo treatment.. Mean plasma concentrations of both MDA and HNE were significantly higher (P<0.0001) in all 43 HD patients than in 20 healthy controls (MDA 2.85+/-0.25 vs 0.37+/-0.03 microM, HNE 0.32+/-0.03 vs 0.10+/-0.01 microM). Comparing the three groups, it was shown that HD patients with a Hb <10 g/dl had significantly higher plasma levels of LPO products (MDA 3.81+/-0.86 microM, HNE 0.45+/-0.07 microM) than HD patients with a Hb >10g/dl (MDA 2.77+/-0.58 UM, HNE 0.25+/-0.05 microM), and than HD patients treated with rHuEpo (MDA 2.50+/-0.12 microM, HNE 0.29+/-0.03 microM). Furthermore, an inverse correlation between plasma concentration of LPO products and haemoglobin levels was seen (r=0.62, P<0.0001).. Radical generation in HD patients might be caused in part by renal anemia itself. Treatment with rHuEpo may decrease radical generation effectively in HD patients due to the increase in the number of red blood cells and blood haemoglobin concentration.

Topics: Adult; Aged; Aged, 80 and over; Aldehydes; Anemia; Erythrocyte Count; Erythropoietin; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Recombinant Proteins; Renal Dialysis; Retrospective Studies

Recombinant human erythropoetin beta; (rHuEPO) has not only an erythropoietic effect but also appears to affect production of cytokines and may improve nutritional status of dialysis patients. Darbepoetin alpha; is a new erythropoiesis-stimulating protein with a threefold longer serum half-life when compared with rHuEPO. The objective of this prospective study was to assess oxidative stress, inflammation, nutrition and hematological response in peritoneal dialysis (PD) patients who were switched from rHuEPO beta to darbepoetin alpha. 12 stable PD patients (6 M, 6 F; mean age 56.2 +/- 15.1 yr.) were evaluated during this study together with 22 healthy volunteers serving as a control group. All patients had been receiving erythropoetin beta subcutaneously once a week before they were reassigned to darbepoetin. The new drug was administered every other week for 6 months, in a dose equivalent to a weekly dose of previously taken rHuEPO. Hematology, iron status and biochemical profiles were evaluated monthly. Markers of oxidative stress: malondialdehyde/ 4-hydroxynoneal (MDA/4HNE), carbonyl groups (CG), oxyLDL and AGEs and markers of inflammation: CRP, TNF alpha, IL-6 were measured on rHuEPO beta before the switch to darbepoetin, and after 1st and 6th month of darbepoetin treatment. The assessment of nutritional status was determined by body mass index (BMI), serum albumin concentration and Subjective Global Assessment (SGA).. Mean levels of Hb and Hct were stable during 6 months of observation and not significantly different from the data observed for on rHuEPO. Nutritional status was good in 9 patients, 3 patients were malnourished at the beginning of this study as assessed by SGA and this status persisted to the end of observation. The levels of markers of oxidative stress and inflammation were statistically higher than in the control group (p < 0.05).. Darbepoetin alpha given subcutaneously once every 2 weeks is effective for the treatment of anemia in PD patients. Less frequent administration of darbepoetin has a biological response similar to weekly administration of rHuEPO.

Topics: Adult; Aldehydes; Anemia; Biomarkers; C-Reactive Protein; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Follow-Up Studies; Hematinics; Humans; Inflammation; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Malondialdehyde; Middle Aged; Nutritional Status; Oxidative Stress; Peritoneal Dialysis; Prospective Studies; Recombinant Proteins; Serum Albumin; Time Factors; Treatment Outcome

Haptoglobin knockout (Hp-/-) mice are more sensitive to phenylhydrazine-induced hemolysis than Hp+/+ mice.. Hemolysis was induced in Hp-/- and Hp+/+ mice using phenylhydrazine. Relative renal tissue damage and function were then assessed.. Hp-/- mice had higher basal levels of renal lipid peroxidation, as evidenced by levels of malonaldehyde and 4-hydroxy-2(E)-nonenal (MDA/HNE). After the administration of phenylhydrazine, levels of 8-hydroxyguanine (but not other products of oxidative DNA damage) were significantly elevated in the renal DNA. There was also increased induction of heme oxygenase-1. The more severe renal damage in Hp-/- mice was also evident in the delayed erythropoietin gene expression and poorer renal clearance of 3H-inulin. This reduction in glomerular filtration function in Hp+/+ and Hp-/- mice could be restored to baseline by vasodilators (prazosin or diazoxide), implicating renal vasoconstriction as a major mechanism of acute renal failure during induced hemolysis. Precipitation of hemoglobin in the kidney was not increased in Hp-/- mice.. Haptoglobin appears to play an important physiological role as an antioxidant, particularly during hemolysis.

Topics: Acute-Phase Reaction; Aldehydes; Animals; Antioxidants; DNA; Erythropoietin; Gene Expression Regulation, Enzymologic; Guanine; Haptoglobins; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Hemoglobins; Hemolysis; Inulin; Kidney; Kidney Function Tests; Lipid Peroxidation; Liver; Malondialdehyde; Membrane Proteins; Mice; Mice, Knockout; Oxidative Stress; Phenylhydrazines; Tritium