Plasma Myeloperoxidase Activity Research Articles

Impaired resolution of inflammation in human chronic heart failure

Lipoxins (LXs) are proresolving and anti-inflammatory eicosanoids whose role in chronic heart failure (CHF) pathogenesis has never been investigated. This study evaluated levels of LXs in CHF patients, its relationship with disease severity and correlation with established CHF biomarkers. The effect of low-dose aspirin [acetylsalicylic acid (ASA)] on the levels of LXs was also studied. Lipoxin A4 (LXA4 ), 15-epi-lipoxin A4 (15-epi-LXA4 ) and myeloperoxidase (MPO) concentration and activity were evaluated by immunoenzymatic and spectrophotometric assays in 34 CHF patients [New York Heart Association (NYHA) functional class I to IV]. B-type natriuretic peptide (BNP), troponin, myoglobin, C-reactive protein (CRP) and uric acid (UA) were also analyzed. Patients were stratified into mild-to-moderate CHF (NYHA, classes I and II) and severe CHF (NYHA classes III and IV). Severe patients had lower plasma LXA4 (0·262±0·034 vs. 0·362±0·039ng/mL, P<0·05) and decreased urinary 15-epi-LXA4 levels (2·28±0·44 vs. 4·88±1·03μg/day, P<0·05) besides exhibiting increased plasma BNP (1464±442 vs. 555±162pg/mL, P<0·05) and MPO activity (45·15±11·56 vs. 15·90± 2·80μmol/min/mgprotein, P<0·05). Plasma LXA4 was inversely correlated with BNP, troponin, myoglobin, CRP, UA and MPO activity. ASA treatment was associated with higher urinary excretion of 15-epi-LXA4 (7·70±1·48 vs. 2·06±0·30μg/day, P<0·05) in mild-to-moderate CHF patients and lower BNP levels in both groups. Higher severity of CHF is associated with reduced levels of LXs. Plasma LXA4 appears to be a valuable marker for risk stratification in CHF. Furthermore, the ASA-related increase in urinary 15-epi-LXA4 suggests enhanced renal synthesis of this eicosanoid and may represent a disregarded benefit of ASA.

Caffeine intake may modulate inflammation markers in trained rats.

Caffeine is presented in many commercial products and has been proven to induce ergogenic effects in exercise, mainly related to redox status homeostasis, inflammation and oxidative stress-related adaptation mechanisms. However, most studies have mainly focused on muscle adaptations, and the role of caffeine in different tissues during exercise training has not been fully described. The aim of this study was therefore, to analyze the effects of chronic caffeine intake and exercise training on liver mitochondria functioning and plasma inflammation markers. Rats were divided into control, control/caffeine, exercise, and exercise/caffeine groups. Exercise groups underwent four weeks of swimming training and caffeine groups were supplemented with 6 mg/kg/day. Liver mitochondrial swelling and complex I activity, and plasma myeloperoxidase (MPO) and acetylcholinesterase (AChE) activities were measured. An anti-inflammatory effect of exercise was evidenced by reduced plasma MPO activity. Additionally, caffeine intake alone and combined with exercise decreased the plasma AChE and MPO activities. The per se anti-inflammatory effect of caffeine intake should be highlighted considering its widespread use as an ergogenic aid. Therefore, caffeine seems to interfere on exercise-induced adaptations and could also be used in different exercise-related health treatments.

Oxidant/Antioxidant Status in Cases of Snake Bite

BackgroundSnake bites are an important cause of mortality and morbidity worldwide, especially in rural areas. ObjectiveThe aim of this study was to investigate serum paraoxonase (PON), arylesterase (ARLY), ceruloplasmin (Cp), and myeloperoxidase (MPO) activity and lipid hydroperoxide (LOOH) and total sulfhydryl group (-SH) levels in patients with snake venom poisoning. MethodsThe study included 49 patients with snake bite envenomation (Group 1) and 39 healthy volunteers as the control group (Group 2). Plasma PON, ARLY, Cp, and MPO activity and LOOH and -SH levels were measured. Laboratory measurements of 20 patients with snake bite envenomation (Group 3) were performed again after treatment. ResultsPON and ARLY activity and -SH levels were significantly decreased in Group 1 compared with those in Group 2. Cp and MPO activity and LOOH levels were significantly elevated in Group 1 compared with those in Group 2. PON and ARLY activity were significantly elevated in Group 3 compared with those in Group 1. Cp and MPO activity and LOOH levels were significantly decreased in Group 3 compared with those in Group 1. ConclusionsPatients with snake bite envenomation had increased oxidants (MPO and LOOH) and decreased antioxidants (PON, ARLY, and -SH). Results obtained in this study demonstrate that snake bites are associated with a shift to oxidative status. Therapy with antioxidants can lead to an increase in the antioxidant defense system, and thus improvements in clinical symptoms.

Scuba Diving Activates Vascular Antioxidant System

The aim was to study the effects of scuba diving immersion on plasma antioxidant defenses, nitric oxide production, endothelin-1 and vascular endothelial growth factor levels. 9 male divers performed an immersion at 50 m depth for a total time of 35 min. Blood samples were obtained before diving at rest, immediately after diving, and 3 h after the diving session. Leukocyte counts, plasma 8oxoHG, malondialdehyde and nitrite levels significantly increased after recovery. Activities of lactate dehydrogenase, creatine kinase, catalase and superoxide significantly increased immediately after diving and these activities remained high after recovery. Plasma myeloperoxidase activity and protein levels and extracellular superoxide dismutase protein levels increased after 3 h. Endothelin-1 concentration significantly decreased after diving and after recovery. Vascular endothelial growth factor concentration significantly increased after diving when compared to pre-diving values, returning to initial values after recovery. Scuba diving at great depth activated the plasma antioxidant system against the oxidative stress induced by elevated pO₂ oxygen associated with hyperbaria. The decrease in endothelin-1 levels and the increase in nitric oxide synthesis could be factors that contribute to post-diving vasodilation. Diving increases vascular endothelial growth factor plasma levels which can contribute to the stimulation of tissue resistance to diving-derived oxidative damage.

Effect of Hemodialysis on Plasma Myeloperoxidase Activity in End Stage Renal Disease Patients.

End stage renal disease (ESRD) patients on hemodialysis (HD) have an increased oxidative stress, with a high risk of atherosclerosis and other co-morbid conditions. Recent studies have suggested that myeloperoxidase (MPO)-mediated oxidative stress may play a role in the pathogenesis of cardiovascular complications in dialysis patients. Furthermore, dialysis treatment 'per se' can aggravate oxidative stress. Hence this study was designed to determine whether HD leads to an alteration in the plasma levels of MPO and malondialdehyde (MDA), a marker of oxidative stress in ESRD patients on maintenance HD. To study the effect of HD, plasma MPO and MDA were determined before and after HD in forty ESRD patients (24 men and 16 women, age between 8 and 71years, median being 40.5years) on maintenance HD. Plasma MPO and MDA were assayed by spectrophotometric methods. Haematological and other biochemical parameters were obtained from patients' case records. Plasma MPO and MDA levels were significantly higher after HD when compared with pre-dialysis levels (p<0.05). There was no correlation between MPO and MDA (r=0.184, p=0.10) and other biochemical parameters (p>0.05). However, there was a significant correlation between MPO and MDA with haemodialysis vintage (p<0.05). In univariate regression analysis duration of HD (β=1.470, p=0.045, β=0.388, p=0.013), was independently associated with MPO and MDA. Although HD is indispensable for survival of patients with ESRD, it is fraught with undesirable side-effects, such as an increase in the plasma MPO and MDA levels. The elevated levels of MPO contribute to the increased oxidative stress as free radicals are produced by the reaction catalyzed by it.

Cholesterol efflux by high density lipoproteins is impaired in patients with active rheumatoid arthritis

ObjectivesReverse cholesterol transport (RCT) is a major antiatherogenic function of high density lipoprotein (HDL). In the current work, the authors evaluated whether the RCT capacity of HDL from rheumatoid arthritis...

Oxidases and oxygenases in regulation of neutrophil redox pathways in Behçet’s disease patients

This study aimed to determine plasma and neutrophil oxidase activities that may contribute to vascular inflammation in Behçet’s disease (BD) patients. Cyclooxygenase (COX), NADPH oxidase and myeloperoxidase (MPO) activity was determined in neutrophils isolated from BD patients and healthy controls. Functional assay of NADPH oxidase was significantly increased in BD patients, both at basal conditions and in response to fMLP stimulation. There was a significant increase in plasma MPO activity in the disease group as compared to controls. Total COX activity was significantly increased in BD neutrophils. The increase in total COX activity was accompanied with enhanced activity of COX-2, differentiated by using the COX-1 isoform-specific inhibitor SC-560. Neutrophil nitrate/nitrite levels showed no significant difference in BD; however, plasma nitrate/nitrite contents in BD patients were significantly greater compared to controls. In conclusion, increased plasma MPO, neutrophil NADPH and COX activities may contribute to intravascular inflammation documented in BD patients.

Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models

Isoforskolin was isolated from Coleus forskohlii native to Yunnan in China. We hypothesize that isoforskolin pretreatment attenuates acute lung injury induced by lipopolysaccharide (endotoxin). Three acute lung injury models were used: situ perfused rat lung, rat and mouse models of endotoxic shock. Additionally, lipopolysaccharide stimulated proinflammatory cytokine production was evaluated in human mononuclear leukocyte. In situ perfused rat lungs, pre-perfusion with isoforskolin (100, and 200 μM) and dexamethasone (65 μM, positive control) inhibited lipopolysaccharide (10 mg/L) induced increases in lung neutrophil adhesion rate, myeloperoxidase activity, lung weight Wet/Dry ratio, permeability-surface area product value, and tumor necrosis factor (TNF)-α levels. In rats, pretreatments with isoforskolin (5, 10, and 20 mg/kg, i.p.) and dexamethasone (5 mg/kg, i.p.) markedly reduced lipopolysaccharide (6 mg/kg i.v.) induced increases of karyocyte, neutrophil counts and protein content in bronchoalveolar lavage fluid, and plasma myeloperoxidase activity. Lung histopathology showed that morphologic changes induced by lipopolysaccharide were less pronounced in the isoforskolin and dexamethasone pretreated rats. In mice, 5 mg/kg isoforskolin and dexamethasone caused 100% and 80% survival, respectively, after administration of lipopolysaccharide (62.5 mg/kg, i.v., 40% survival if untreated). In human mononuclear leukocyte, isoforskolin (50, 100, and 200 μM) and dexamethasone (10 μM) pre-incubation lowered lipopolysaccharide (2 μg/mL) induced secretion of the cytokine TNF-α, and interleukins (IL)-1β, IL-6, and IL-8. In conclusion, pretreatment with isoforskolin attenuates lipopolysaccharide-induced acute lung injury in several models, and it is involved in down-regulation of inflammatory responses and proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8.

Nitric oxide and renal protection in morphine-dependent rats

Morphine treatment for 5 days protects heart against ischemia–reperfusion (IR) injury. This study evaluated the involvement of nitric oxide (NO) in morphine-induced renal protection. Three weeks after right nephrectomy, increasing doses of morphine were administered (20–30 mg kg − 1 day − 1 , 5 days) to develop dependence in rats. The left kidney underwent 45-min ischemia and 24-h reperfusion. Some rats were pretreated with naloxone (5 mg kg − 1 ) or L-NAME (20 mg kg − 1 ). In one group, IR was induced 24 h after the last dose of morphine during the withdrawal period. Plasma nitrite/nitrate levels and serum creatinine and BUN were measured. Creatinine clearance and fractional excretion of sodium (FE Na) were calculated. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and inducible NO synthase (iNOS) expression were determined and histopathology was studied in the left kidney. IR increased serum creatinine and BUN, plasma NO ( p < 0.01), FE Na, iNOS expression ( p < 0.001), MPO activity, MDA level, and tissue damage and decreased creatinine clearance. Morphine decreased plasma NO ( p < 0.05 vs IR), serum creatinine and BUN ( p < 0.01), FE Na, MPO activity, MDA level, iNOS expression, and tissue damage ( p < 0.05), but increased creatinine clearance ( p < 0.05). Pretreatment with naloxone significantly increased NO production and iNOS expression in morphine-treated rats after IR ( p < 0.01 vs morphine dependence + IR). Pretreatment with L-NAME in morphine-treated rats decreased NO production (10.7 ± 1.9, p < 0.01 vs morphine dependence + IR) but could not change iNOS expression after IR. Both naloxone and L-NAME significantly abolished the protective effects of morphine dependence on functional and histological factors. The protective effect of morphine dependence on serum creatinine, BUN, FE Na, and creatinine clearance persisted during the withdrawal period, whereas iNOS expression decreased. NO production was not decreased during the withdrawal period ( p > 0.1 vs morphine dependence + IR group). Morphine dependence provided renal protection in the acute phase and during withdrawal. Excessive increase or decrease in NO production abolished the effects of morphine, which suggested a role for balanced NO production and iNOS expression.

A myeloperoxidase promoter polymorphism is independently associated with mortality in patients with impaired left ventricular function

Circulating levels of myeloperoxidase (MPO), a heme enzyme released upon activation of polymorphonuclear neutrophils, predict adverse outcome in patients with impaired left ventricular (LV) function. The MPO −463 G/A promoter polymorphism (rs 2333227) regulates MPO transcription, with the G allele being linked to increased protein expression. The aim of this study was to assess the prognostic information derived from the −463 G/A MPO polymorphism on outcomes of patients with impaired LV function. The −463 G/A promoter MPO genotype as well as MPO plasma levels were determined in 116 patients with impaired LV function. Patients were prospectively followed for a median of 1050 days. The GG genotype was associated with a decrease in overall survival (χ 2 5.80; p = 0.016). This association remained after multivariate adjustment for plasma levels of NT-proBNP, creatinine, hsCRP, and MPO; leukocyte count; and LV function (hazard ratio 3.16 (95% CI 1.17–8.53), p = 0.024) and for classical cardiovascular risk factors (hazard ratio 2.88 (95% CI 1.13–7.33), p = 0.026). Interestingly, we observed no association of the MPO polymorphism with total MPO protein concentration or MPO activity in plasma. The −463 G/A MPO polymorphism is linked to adverse clinical outcome of patients with impaired LV function. Further studies are needed to elucidate the value of this polymorphism for risk stratification.

Postprandial serum induces apoptosis in endothelial cells: Role of polymorphonuclear-derived myeloperoxidase and metalloproteinase-9 activity

Postprandial state is a pro-inflammatory condition associated with a transient impairment of endothelial function. Recent evidence suggests that myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9) are involved in the pathogenesis of inflammatory vascular diseases such as atherosclerosis. The present study was carried out to investigate whether a fat meal induces polymorphonuclear (PMN) activation and increases the plasma activity of MPO and MMP-9 and whether postprandial serum exerts pro-apoptotic effects on endothelial cells. Fifteen healthy young men underwent a high-fat challenge containing 60 g butter. Blood samples were drawn before, and 1, 2, and 4 h after the meal. Leukocyte reactive oxygen species (ROS) production, plasma MPO and MMP-9 activity, endothelial-derived soluble CD146 levels, and advanced oxidation protein product (AOPP) levels were determined. Human umbilical vein endothelial cells (HUVECs) were treated with human sera to evaluate mitochondrial membrane potential, ROS production, annexin PI staining, and caspase-3 activity. Triglycerides, ROS production, MPO activity, AOPP levels, pro-MMP-9 zymographic activity, and soluble CD146 levels significantly increased during the 4 h after the test meal. Postprandial serum significantly decreased the mitochondrial membrane potential, and increased the rate of ROS production, the percentage of annexin-positive HUVECs, and caspase-3 activity. A strong relationship was observed between postprandial increase in PMN-derived MPO and pro-MMP-9 activity, and the increased rate of apoptosis of endothelial cells exposed to postprandial serum. Data show that postprandial serum exerts pro-apoptotic effects on endothelial cells. The close relationships between markers of endothelial cell apoptosis and MPO and pro-MMP-9 activity suggest that the latter may contribute to the development of fat meal induced endothelial damage.

Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia-reperfusion injury in mouse kidney

The mechanisms involved in renal ischemia-reperfusion injury (IRI) are complex and appear to involve the early participation of bone marrow-derived cells. T lymphocytes participate in the pathogenesis of IRI. Sphingosine 1-phosphate (S1P) induces peripheral T cell depletion. Therefore, we hypothesized that S1P1 receptor activation protects kidney from IRI. FTY-720, a non-receptor-selective sphingosine analog, was given intraperitoneally to C57BL/6 mice, and animals were subjected to ischemia for 32 min followed by reperfusion for 24 h. Plasma creatinine, blood count, myeloperoxidase (MPO) activity, and renal histology were determined. IRI led to a marked increase in plasma creatinine, MPO activity, leukocyte infiltration, and vascular permeability. FTY-720 significantly decreased plasma creatinine in a dose-response manner with a maximal reduction of approximately 73 and approximately 69% with doses of 240 and 48 microg/kg, respectively. MPO, leukocyte infiltration, vascular permeability, and peripheral blood lymphocyte counts were markedly decreased with FTY-720 treatment. The protective effect of FTY-720 was reversed with VPC-44116, a selective S1P1 receptor antagonist. Furthermore, SEW-2871, a selective S1P1 agonist, significantly decreased plasma creatinine in a dose-response manner with a maximal reduction of approximately 70% with a dose of 10 mg/kg. Analysis of kidneys by light microscopy revealed minimal histological signs of ischemic injury with FTY-720 or SEW-2871 treatment compared with the vehicle group. Using RT-PCR, we found a time-dependent increase in the S1P1 mRNA expression following IRI that begins after 2 h with the maximum expression at approximately 4 h. We conclude that the protective effect of FTY-720 is due primarily to activation of S1P1 receptors. The mechanism of protection is not known but may be related to peripheral lymphocyte depletion or direct effects on kidney cells expressing S1P1 receptor.

Protein oxidation status in patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease with unknown aetiology. Since various functions of neutrophils are increased in AS, neutrophil activation-mediated oxidative stress may have an important role in the pathogenesis of AS. Therefore, the importance of neutrophil activation as the main source of oxidative stress was investigated in patients with AS. Forty-one patients with AS, divided into active and inactive groups according to their CRP and ESR, and 30 healthy volunteers were entered into the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the visual analogue scale (VAS) were also used in all patients before the study. In addition, the patients were evaluated according to spinal involvement and peripheral involvement. Plasma myeloperoxidase (MPO) activity, representing neutrophil activation, and oxidative stress biomarkers, such as advanced oxidation protein products (AOPP) and thiol levels, were measured. There were significant increases in plasma MPO activity and AOPP but decreases in thiol levels in the total AS patient group and in the subgroups, compared with controls. All parameters, except thiol, were higher in active and peripheral involvement groups than in the inactive and spinal patients, respectively; but the highest levels were observed in the peripheral subgroup. In addition, AOPP was found to be positively correlated with ESR, CRP and BASDAI in the total patient group and with white blood cell and neutrophil count in the peripheral involvement subgroup. BASDAI was positively correlated with VAS, ESR and CRP; but MPO was negatively correlated with thiol/albumin ratio, both in total and active AS patients. Negative correlations were also observed between albumin and ESR, and between CRP and neutrophil counts in the peripheral subgroup. This is the first study suggesting neutrophil-MPO-hypochlorous acid-mediated AOPP formation in AS. Therefore, active neutrophils and chlorinated oxidants of neutrophil origin may be considered to be important factors in the pathogenesis of AS which are related to oxidative stress, notably protein oxidation.

The effects of dialyzer reuse on plasma antioxidative mechanisms in patients on regular hemodialysis treatment

The effects of antioxidative mechanism are known to be reduced in patients on regular hemodialysis treatment (RHT). The data about the effects of reuse on antioxidative mechanisms are limited. Twelve patients on RHT (age range: 16–50 years) were included in the study. The basal and after 4 months of dialyzer reuse period, plasma antioxidant activity (AOA), myeloperoxidase (MPO) activity, ceruloplasmin (Cp), copper (Cu), transferrin (TF), and sulphydryl group (SH) levels were detected. The basal plasma AOA (110.92 ± 17.19 μl), TF (1.23 ± 0.23 g/1), and SH (307.11 ± 51.81 μmol/1) levels were lower than the levels of the control subjects (73.75 ± 9.07 μl, 2.38 ± 0.25 g/1, 690.59 ± 84.18 μmol/10) ( p < .001). The basal Cp (0.47 ± 0.08 g/1) and MPO activity (86.31 ± 9.57 U/1) levels were higher than the levels of the control subjects (0.34 ± 0.07 g/1 and 65.90 ± 7.28 U/1) ( p < .001). The basal Cu levels (1.19 ± 0.24 mg/1) were similar to the levels of the control subjects (1.11 ± 0.13 mg/1) ( p > .05). The difference between plasma AOA (83.33 ± 14.71 μ1), Cp (0.38 ± 0.08 g/1), and MPO activity (64.43 ± 10.01 U/1) after the reuse period and the control values were not statistically significant ( p > .05). The TF (1.87 ± 0.15 g/1) levels after the reuse period were significantly lower than the control values ( p < .001), although the levels were increased after the reuse period. Our findings may indicate some beneficial effects of hemodialyzer reuse process on plasma antioxidative mechanisms in patients on RHT.