Serum Myeloperoxidase Levels Research Articles

A comparative study of serum myeloperoxidase activity in type 2 diabetes and diabetic nephropathy

Inflammatory burden is high in End Stage Renal Disease (ESRD) patients. In Diabetic ESRD patients, the balance between pro- and anti-oxidant activities is shifted towards an oxidative stress. Myeloperoxidase (MPO), a bactericidal enzyme plays an active role in induction and evolution of the endothelial dysfunction associated with Type 2 Diabetes Mellitus (DM). However, whether MPO can serve as a marker in diabetic ESRD patients is doubtful. Hence, the present study was undertaken. The Fasting Blood Glucose (FBG), Serum Creatinine, Blood Urea Nitrogen (BUN) and Serum Myeloperoxidase levels were estimated in three different groups with 30 subjects each. The Control group includes healthy individuals, group I constitutes Type 2 diabetes with no nephropathy and group II includes Type 2 diabetes with nephropathy patients. Glomerular Filtration Rate (GFR) was calculated using Cockcroft Gault formula corrected for the Body Surface Area. Statistical software, namely, SPSS 15.0, Stata 8.0, MedCalc 9.0.1 and Systat 11.0 were used for the analysis of the data and Microsoft word and Excel have been used to generate graphs, tables etc. Reference Ranges for MPO were established in our study. An increase in MPO levels was noticed in Group I, whereas a differential behaviour of MPO levels was noted in group II. Uremic diabetic nephropathy patients with a low MPO level may be at a lesser risk for any cardiac event compared to those uremic patients with high MPO levels. Hence, MPO may be taken as a biomarker to predict coronary events in diabetic ESRD.

The effect of N-acetylcysteine on biomarkers for radiation-induced oxidative damage in a rat model.

Our study aimed to investigate the potential radioprotective effects of N-acetylcysteine (NAC) by comparing its biochemical effects with those of WR-2721, as a representative of clinically used radioprotectors, in preventing oxidative damage caused by gamma irradiation (single dose, 6Gy) in normal rat tissue. The rats (n=40) were divided randomly and equally into 4 groups:Control (C), Radiation (R), R+NAC (received irradiation and 1,000 mg/kg NAC) and R+WR-2721 (received irradiation and 200 mg/kg WR-2721) rats. Liver tissues and blood samples were harvested and utilized for reduced glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) detection. Serum and tissue GSH levels of R rats decreased compared to those of other groups (p<0.01). Tissue MDA levels of R+NAC and R+WR-2721 rats decreased compared to R rats (p<0.01; p<0.05, respectively). Tissue MPO activities of R+NAC and R+WR-2721 rats were higher than those of R rats (p<0.001). Serum MPO levels of R+WR-2721 rats were lower than those of C rats and R rats (p<0.01, p<0.001, respectively). In conclusion, the study suggests that the radioprotective effect against radiation-induced oxidative damage of NAC may be similar to that of WR-2721.

Influence of maternal nicotine exposure on neonatal rat oxidant–antioxidant system and effect of ascorbic acid supplementation

There have been a few studies that examined the oxidative stress effects of nicotine during pregnancy and lactation. We aimed to determine the adverse effects of maternal nicotine exposure during pregnancy and lactation on oxidant-antioxidant system, and to determine a protective effect of ascorbic acid (Asc). Gravid rats were assigned into four groups. In Group 1, pregnant rats received 6-mg/kg/day nicotine subcutaneously during pregnancy from 1 to 21 days of gestation and lactation (until postnatal day 21). Group 2 received nicotine and Asc for the same period. In Group 3, the rats received nicotine during lactation. Control pregnant rats (Group 4) received only saline subcutaneously. Serum malondialdehyde (MDA), myeloperoxidase (MPO), and superoxide dismutase (SOD) levels were determined at 21 days of age. Nicotine exposure decreased birth weight and pregnancy weight gain. MDA values of the rat pups exposed to nicotine in both Groups 1 and 2 were higher than those of control and Group 3. SOD and MPO values of the groups were similar. Mean birth weight and serum MDA levels of Groups 1 and 2 were similar. Nicotine exposure via placental transfer increases oxidative stress as manifested by an increase in MDA level. Asc supplementation does not prevent the adverse effects of maternal nicotine exposure.

Plasma levels of myeloperoxidase are not elevated in patients with stable coronary artery disease

Background Plasma and serum levels of myeloperoxidase (MPO), a redox-active hemoprotein released by polymorphonuclear neutrophils (PMN) upon activation, is now recognized as a powerful prognostic determinant of myocardial infarction in patients suffering acute coronary syndromes. However, there is limited information on whether systemic MPO levels are also elevated and of discriminating value in patients with stable coronary artery disease (CAD) representing different ethnic groups. Methods Plasma levels of MPO and traditional CAD risk factors were quantified in African American and Caucasian patients ( n = 557) undergoing elective coronary angiography. Results MPO levels did not differ significantly between patients with or without CAD [421 pM (321, 533) vs. 412 pM (326, 500), p > 0.05]. MPO levels were similar across ethnicity and gender, and correlated positively with CRP and fibrinogen levels ( r = 0.132, p = 0.002 and r = 0.106, p = 0.011, respectively). Conclusion In conclusion, plasma MPO levels were not elevated in patients with stable CAD, suggesting that systemic release of MPO is not a characteristic feature of asymptomatic CAD.

Prognostic Value of Admission Myeloperoxidase Levels in Patients With ST-Segment Elevation Myocardial Infarction and Cardiogenic Shock

Inflammation plays a critical role in acute myocardial infarction. One inflammatory marker is myeloperoxidase (MPO). Its role as a predictor of in-hospital death in patients with ST-segment elevation myocardial infarction (STEMI) presenting with cardiogenic shock (CS) is unclear. Therefore, the aim of this study was to investigate the role of MPO as a predictor of in-hospital death in patients with STEMIs presenting with CS and treated with primary percutaneous coronary intervention. In 38 consecutive patients with CS complicating STEMIs who were treated with primary percutaneous coronary intervention, serum MPO levels were measured at coronary care unit admission using a commercially available enzyme-linked immunosorbent assay. The primary study end point was in-hospital cardiac death. Among the 38 patients included in the study, 20 died during their coronary care unit stays, whereas 18 survived. Compared with patients who survived, patients who died showed, at coronary care unit admission, higher serum MPO levels (81 +/- 28 vs 56 +/- 23 ng/ml, p <0.006). After controlling for different baseline clinical, laboratory, and angiographic variables, baseline serum MPO level was an independent predictor of in-hospital mortality on multivariate analysis (odds ratio 3.9, 95% confidence interval 1.8 to 7.5, p <0.001). In conclusion, admission MPO concentration is an independent predictor of in-hospital mortality in patients with STEMIs presenting with CS.

Neutrophil Activation in Patients with ASA-Induced Urticaria

The pathogenic mechanism of acetyl salicylic acid (ASA)-induced urticaria (AIU) is not fully understood. We compared the levels of neutrophil activation and related cytokines in patients with ASA-intolerant acute urticaria (AIAU) and ASA-intolerant chronic urticaria (AICU). A total of 51 patients with AIAU, 88 patients with AICU, and 102 normal controls (NC) were enrolled in this study. The serum levels of myeloperoxidase (MPO), interleukin-8 (IL-8), and IL-18 were compared among the three groups. The serum levels of MPO were highest in the AIAU group, followed by the AICU and NC groups, and the serum levels of IL-18 were significantly higher in the AIAU and AICU groups than in NC group. Within the AIU groups, significant correlations were noted between the levels of MPO and IL-8, and IL-8 and IL-18. In conclusion, neutrophil activation, which was associated with the levels of IL-8 and IL-18 in the AIAU group, may be involved in the pathogenic mechanism of AIU. A role for IL-18 in the pathogenesis of AIU is also suggested.

Oxidative stress parameters in patients with slow coronary flow

We investigated the probable role of free-radical damage in the pathogenesis of slow coronary flow (SCF) by using oxidative stress parameters. Sixty-four patients with angiographically proven SCF and 63 patients with normal coronary flow (NCF) pattern with similar risk profiles were enrolled in this study. We measured erythrocyte superoxide dismutase (SOD), reduced glutathione (GSH), serum malondialdehyde (MDA), catalase and myeloperoxidase (MPO) levels in all subjects. There were statistically significant differences in the levels of erythrocyte SOD, GSH and serum MDA between the 2 groups. Serum MDA (P = 0.003) and erythrocyte SOD levels (P = 0.0001) were increased in the SCF group. The level of erythrocyte GSH (P = 0.010) was lower in patients with SCF. There were no differences between the groups' serum catalase (P = 0.682) and MPO levels (P = 0.070). Our data showed that in patients with SCF, serum MDA and erythrocyte SOD levels were increased while erythrocyte GSH levels were decreased significantly, compared with NCF patients. These results indicate that free-radical damage may play a role in the pathogenesis of SCF.

Valor preditivo da mieloperoxidase na identificação de pacientes de alto risco admitidos por dor torácica aguda

Myeloperoxidase (MPO) is a highly expressed enzyme due to leukocyte activation, with multiple atherogenic actions, including LDL cholesterol oxidation, and is related to the instability of atherosclerotic plaque. It is a predictor of adverse events in healthy individuals, patients with heart disease or those undergoing chest pain investigations. To analyze the contribution of MPO to identify patients with acute chest pain, non-ST elevation ECG and at high risk for in-hospital adverse events. Patients presenting acute chest pain and a non-ST elevation ECG, were admitted to the hospital and submitted to serum MPO level measurements and a structured examination protocol. From a cohort of 140 patients, 49 (35%) were diagnosed with acute coronary syndrome, of which 13 patients (9.3%) were diagnosed with non-ST elevation acute myocardial infarction (AMI) (troponin I >1.0 ng/mL). The best MPO cut-off point for AMI was identified as >100 pM using the ROC curve (AUC=0.662; CI 95%=0.532-0.793) revealing elevated sensitivity (92.3%) and negative predictive value (98.1%), however with low specificity (40.2%). In the multivariate analysis, MPO proved to be the only independent variable to diagnose AMI in evolution, with an odds ratio of 8.04 (p=0.048). In patients with acute chest pain and no ST elevation, high MPO levels upon admission to the hospital are an important tool to predict in-hospital adverse events, with an odds ratio of eight for the diagnosis of AMI.

Primed polymorphonuclear leukocytes constitute a possible link between inflammation and oxidative stress in hyperlipidemic patients

BackgroundOxidative stress (OS) and chronic inflammation are involved and contribute to the development of atherosclerosis. Primed polymorphonuclear leukocytes (PMNLs) are a possible source for superoxide radicals and inflammatory mediators, hence can promote OS and inflammation. The involvement of primed PMNLs in clinical states associated with high risk for developing cardiovascular disease and atherosclerosis, such as hypertension, renal failure and diabetes has been described, however, little is known about PMNLs characteristics in hyperlipidemic patients. MethodsHyperlipidemic patients and healthy control (HC) subjects were enrolled in this cross-sectional study. PMNL priming was estimated by measuring the rate of superoxide release and by levels of membrane CD11b. PMNL priming and myeloperoxidase (MPO) levels served as OS indices. Inflammation was linked to peripheral white blood cells and PMNL counts and to apoptosis. Systemic inflammation was estimated by blood levels of fibrinogen, C-reactive protein (CRP), transferrin and albumin. PMNL priming and inflammation parameters were related to the severity of hyperlipidemia. ResultsPMNLs from hyperlipidemic patients are primed compared to HC. A decrease in PMNL-MPO levels with increased levels of serum MPO were found in hyperlipidemic patients. Leukocyte counts tended to be higher in hyperlipidemic patients with increased PMNL apoptosis. PMNL priming and fibrinogen levels correlated positively with the severity of hyperlipidemia (r=0.32, P=0.02 for CD11b vs. cholesterol and r=0.38, P=0.009 for CD11b vs. LDL-c; r=0.35, P=0.01 for fibrinogen vs. cholesterol and r=0.3, P=0.03 for superoxide release vs. LDL-c). ConclusionPMNLs are primed in hyperlipidemic patients contributing to OS and inflammation in these patients. This study highlights primed PMNLs as an additional risk factor for promoting atherosclerosis in hyperlipidemic patients.

Serum Myeloperoxidase Levels Are Associated With the Future Risk of Coronary Artery Disease in Apparently Healthy Individuals: The EPIC-Norfolk Prospective Population Study

We evaluated whether serum myeloperoxidase (MPO) levels are associated with the risk of future development of coronary artery disease (CAD) in apparently healthy individuals. An enzyme of the innate immune system, MPO exhibits a wide array of proatherogenic effects. These include induction of oxidative damage to low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and promotion of plaque vulnerability. Recent studies revealed that MPO independently predicts adverse outcomes in patients with chest pain or suspected acute coronary syndrome. Myeloperoxidase was measured in baseline samples of a case-control study nested in the prospective EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk population study. Case subjects (n = 1,138) were apparently healthy men and women who developed CAD during 8-year follow-up. Control subjects (n = 2,237), matched for age, gender, and enrollment time, remained free of CAD. The MPO levels were significantly higher in case subjects than in control subjects and correlated with C-reactive protein (CRP) (rho = 0.25; p < 0.001) and white blood cell count (rho = 0.33; p < 0.001). Risk of future CAD increased in consecutive quartiles of MPO concentration, with an odds ratio (OR) of 1.49 in the top versus bottom quartile (95% confidence interval [CI] 1.20 to 1.84; p < 0.001). After adjustment for traditional risk factors, the OR in the top quartile remained significant at 1.36 (95% CI 1.07 to 1.73). Elevated MPO levels (>728 pmol/l) similarly predicted increased risk of future CAD among participants with either LDL-cholesterol <130 mg/dl, HDL-cholesterol >50 mg/dl, or CRP <2.0 mg/l (OR 1.52 [95% CI 1.21 to 1.91], 1.59 [95% CI 1.24 to 2.05], and 1.42 [95% CI 1.14 to 1.77)], respectively). Elevated MPO levels predict future risk of CAD in apparently healthy individuals. This study suggests that inflammatory activation precedes the onset of overt CAD by many years.

Trafficking of QD‐Conjugated MPO‐ANCA in Murine Systemic Vasculitis and Glomerulonephritis Model Mice

In systemic vasculitis, the serum level of myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA) is significantly elevated with the progression of disease. We have established a model of murine systemic vasculitis by administration of MPO-ANCA and fungal mannoprotein to C57BL/6 mice. We examined the role of MPO and MPO-ANCA in the pathogenesis of glomerulonephritis and systemic vasculitis in this model using quantum dots (QDs). We demonstrated that QD-conjugated MPO-ANCA (ANCA-QD) visualized the translocation of MPO on the neutrophil membrane surface after stimulation with proinflammatory cytokines. We also observed that MPO translocation on neutrophils in both patients with rapid progressive glomerulonephritis and these model mice without any stimulation, suggesting that MPO translocation is certain to contribute to the development of glomerular lesion. In addition, blood flow on the kidney surface vessel was significantly decelerated in both SCG/Kj mice and this model, suggesting that ANCA induces the damage of blood vessel. These results indicate that MPO-ANCA and surface-translocated MPO on the activated neutrophils coordinately plays essential roles in the initial steps of the glomerulonephritis.

Serum myeloperoxidase in cystic fibrosis patients receiving systemic antibiotics

Serial serum myeloperoxidase was determined in 27 cystic fibrosis patients with chronic endobronchial Pseudomonas aeruginosa infection over the course of 1 y. The effect of repeated courses of antibiotic therapy on mean serum myeloperoxidase levels was significant (p = 0.034). Serial serum myeloperoxidase may help to guide therapy for pulmonary exacerbations.

Myeloperoxidase predicts risk of vasculopathic events in hemizgygous males with Fabry disease

Fabry disease results in a global vasculopathy leading to early-onset stroke and renal and cardiac failure. We found that random myeloperoxidase in serum and plasma was significantly elevated in 73 consecutive male patients with Fabry disease. Random serum myeloperoxidase level in men predicted the risk of a Fabry vasculopathy-related event in subsequent years. Long-term enzyme replacement therapy did not reduce myeloperoxidase level or eliminate the risk of vasculopathic events.

Upregulation of myeloperoxidase in patients with opticospinal multiple sclerosis: Positive correlation with disease severity

To clarify the role of myeloperoxidase (MPO) in multiple sclerosis (MS), we measured serum MPO levels in 86 Japanese patients with relapsing remitting MS, 47 with opticospinal MS (OSMS) and 39 with conventional MS (CMS), and 85 healthy subjects by sandwich enzyme immunoassays and analyzed relationships with clinical features. We found a significant increase in serum MPO in OSMS patients at relapse and remission, and in CMS patients at remission compared with controls. By logistic regression analysis, the clinical variable associated with high level of MPO at remission in OSMS patients (higher than the mean ± 2 S.D. of healthy controls) was only Kurtzke's Expanded Disability Status Scale (EDSS) score in blood sampling ( p = 0.0245); that is, a greater EDSS scores in the high MPO group, whereas in CMS none were associated. The results of our study suggest that MPO levels in remission are related with severe tissue destruction in OSMS.

Serum Myeloperoxidase and Mortality in Maintenance Hemodialysis Patients

During inflammation, myeloperoxidase (MPO) is released, for which its measurement in systemic circulation may be used as an index of leukocyte activation and oxidant stress. MPO levels correlate with angiographic evidence of coronary atherosclerosis and cardiovascular events in subjects with chest pain within the general population. We hypothesized that serum MPO levels are associated with adverse clinical outcomes in maintenance hemodialysis (MHD) patients. MPO levels were determined in serum samples from 356 MHD patients at the start of a 3-year cohort. Patients (46% women, 28% blacks, 54% with diabetes) were 54.6 +/- 14.6 (SD) years old and had undergone MHD for a median period of 26 months. Measured serum MPO level was 2,005 +/- 1,877 pmol/L (median, 1,444 pmol/L; interquartile range, 861 to 2,490 pmol/L). MHD patients with greater total body fat had greater MPO levels. MPO level had statistically significant (P < 0.01) and positive correlations with values for serum C-reactive protein (CRP; r = +0.15), interleukin 6 (IL-6; r = +0.23), tumor necrosis factor alpha (TNF-alpha; r = +0.21), and white blood cell count (r = +0.21). A death hazard ratio for each 1,000-pmol/L increase in serum MPO level was 1.14 (95% confidence interval [CI], 1.03 to 1.26; P = 0.01) after controlling for age, race (black), diabetes mellitus, dialysis vintage, Charlson comorbidity score, history of previous cardiovascular disease, blood hemoglobin level, and serum concentrations of albumin, CRP, IL-6, and TNF-alpha. After dividing MPO values into 3 equal groups (tertiles), the death hazard ratio of the highest tertile (versus the middle tertile) was 1.82 (95% CI, 1.07 to 3.10; P = 0.03). Serum MPO levels correlate with levels of markers of inflammation and prospective mortality risk in MHD patients.

Combined Therapy of Teicoplanin and Caffeic Acid Phenethyl Ester (CAPE) in the Treatment of Experimental Mediastinitis in the Rat

Post-sternotomy mediastinitis affects 1-3% of patients undergoing cardiac surgery and is lethal in 10-47% of these patients.We investigated the effect of an antioxidant/anti-inflammatory agent, caffeic acid phenethyl ester (CAPE), in the attenuation of inflammatory response induced by methicillin-resistant Staphylococcus aureus (MRSA) infection in a rat experimental mediastinitis model. Rats, divided into six equal groups, received MRSA precolonized stainless steel wire pieces implanted into their mediastinal spaces. Control group and CAPE control group received saline and CAPE 10 μmol/kg.day−1 respectively, where Group A received a single dose of teicoplanin 24 mg/kg i.m. for the first day and then 12 mg/kg.day−1. Group B received teicoplanin as in Group A plus CAPE 10 μmol/kg. day−1 intra-peritoneally. Group C received teicoplanin 60 mg/kg i.m. for the first day and then 30 mg/kg.day−1 and Group D received teicoplanin as in Group C plus CAPE 10 μmol/kg.day−1. By the end of 14 days rats were sacrificed and serum malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), urea and creatinine levels were evaluated. Mediastinal organ tissues were collected for histopathological analysis.Infection rates in all the drug-treated groups were lower than the control groups (P = 0.002) but statistical significance was attained only between the groups A and D (P = 0.018). In connective tissues and the peribronchial area polymorphonuclear leukocytic (PNL) infiltration in the treatment groups, although becoming very close, did not reach statistical significance (P = 0.053, P = 0.075, respectively). PNL infiltration especially in the peribronchial tissues of the Group B animals was found to be significantly less than the Control and CAPE Control groups with P values of 0.013 and 0.010, respectively. MDA and MPO levels were significantly lower in the treatment groups (P < 0.001 and P < 0.001 respectively). Levels of the degradation products of NO were lower in treatment groups compared to two control groups (P = 0.003, P = 0.005). NO levels in Group D were lowest among all treatment groups (P = 0.001).It has been demonstrated that although bacterial colonization can be controlled in mediastinitis, the inflammatory response persists. The combination of an antioxidant / anti-inflammatory agent, CAPE, added to standard antibiotic therapy might be effective in the treatment of post-sternotomy mediastinitis due to MRSA.

The effect of atorvastatin on serum myeloperoxidase and CRP levels in patients with acute coronary syndrome

Background Inflammation is involved in the atherogenesis and pathogenesis of acute coronary syndrome (ACS). As the acute-phase reaction proteins in ACS, myeloperoxidase (MPO) and C-reactive protein (CRP) may play critical roles. Anti-inflammation may be one of benefits of statin drugs in ACS. Studies have showed that statins can suppress serum CRP concentrations. However, whether statins also reduce serum MPO concentrations in patients with ACS is unknown. Methods Seventy-eight patients with ACS were randomly separated into Group A and Group B, the patients in Group A receiving conventional therapy, which include no cholesterol-lowering drugs, + atorvastatin (10 mg/day, n = 40), the patients in Group B receiving conventional therapy ( n = 38). The serum concentrations of MPO were measured by enzyme-linked immunosorbent assay (ELISA) and CRP were measured by turbidimetric immunoassay. Results Serum concentrations of MPO were significantly lower after 1-week therapy in both groups of patients [Group A from 590 ± 168 to 496 ± 154 μg/l, Group B from 570 ± 165 to 521 ± 153 μg/l; P < 0.01, respectively]. Serum concentrations of CRP also were markedly lower than pretreatment [Group A from 6.56 ± 1.87 to 5.14 ± 2.07 mg/l; Group B from 6.36 ± 1.94 to 5.45 ± 1.90 mg/l, P < 0.05, respectively]. Compared with conventional therapy alone, atorvastatin significantly further reduced serum MPO [ P = 0.014] and CRP concentrations [ P = 0.032]. There were no correlations detected between the reduction of MPO and CRP ( r = 0.124, P = 0.068). Conclusions Atorvastatin reduced serum MPO and CRP concentrations in patients with ACS. These effects may explain some clinical benefits of statins in the treatment of these patients.

The Effect of Aminoguanidine on Blood and Tissue Lipid Peroxidation in Jaundiced Rats With Endotoxemia Induced With LPS

Obstructive jaundice (OJ) is a severe condition that leads to several complications. One of the important problems in OJ is the increased incidence of endotoxemia, which is the result of bacterial translocation (BT) and defective host immune response. Lipid peroxidation (LP) is an important problem in OJ and sepsis in which nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity are increased and antioxidative activity is decreased. Formation of peroxynitrite (ONOO−) anion leads to cellular damage and apoptosis. In this experimental study, we explore the effect of specific iNOS inhibitor aminoguanidine (AG) on blood and tissue (liver and renal) LP and iNOS levels in jaundiced rats with endotoxemia induced with lipopolysaccharide (LPS). Rats were randomized into six groups; group A, sham; group B, obstructive jaundice (OJ); group C, OJ + LPS; group D, OJ + AG; group E, OJ + LPS + AG; group F, OJ + AG + LPS. Serum malondialdehyde (MDA) and serum myeloperoxidase (MPO) activity and liver and renal tissue MDA, MPO, and Na+/K+-ATPase activity levels were detected in biochemical methods. Liver and renal tissue iNOS levels were examined immunohistopathologically. Serum and tissue MDA and MPO levels and tissue iNOS expression were increased significantly in groups B, C, and E, while tissue ATPase levels were decreased significantly in the same groups. In the group treated with AG (group D), serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. In group F, if AG was administrated before LPS, we observed that serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. Thus, our study showed that AG had a protective effect when it was administrated before LPS, but it failed to prevent tissue iNOS expression and LP if there was established endotoxemia in OJ.

Investigation of protein oxidation and lipid peroxidation in patients with rheumatoid arthritis

We aimed to determine the importance of neutrophil activation and the source of oxidative stress in the pathogenesis of rheumatoid arthritis (RA) by quantification of advanced oxidation protein products (AOPP) and total thiol levels as markers of oxidative protein damage, malondialdehyde (MDA) levels as a marker of lipid peroxidation and myeloperoxidase (MPO) activity as a marker of neutrophil activation in patients with RA. Fifty-seven rheumatoid arthritis patients were included in the study and sub-grouped according to disease activity (active, n = 31; inactive, n = 26) and compared with healthy controls (n = 25). Serum MPO activity, AOPP, MDA, and thiol levels were measured by an enzymic spectrophotometric method. Serum MPO activity (p < 0.001), AOPP (p < 0.001), MDA (p < 0.001) and levels of thiol (p < 0.002), were higher in the patient group than the controls. Active and inactive RA groups were compared with the control group and there were significant differences between each parameter. MPO activity, AOPP, MDA and thiol levels were significantly higher in both active and inactive RA patients than the controls. On the other hand, when a comparison was made between active and the inactive stage, a statistically significant difference was present only in MDA (p < 0.05) and AOPP levels (p < 0.05). There was also a significant positive correlation between all parameters. These data strongly suggest that neutrophils, which constitute the most important source of chlorinated oxidants due to their high MPO content, may be involved in serum AOPP formation and therefore the production of a novel class of pro-inflammatory mediators of oxidative stress in RA patients and that protein oxidation could play an important role in the pathogenesis of RA as does lipid peroxidation.

The Effect of N-Acetylcysteine on Pulmonary Lipid Peroxidation and Tissue Damage

We aimed to investigate the effect of N-acetylcysteine (NAC) on pulmonary lipid peroxidation and tissue damage in experimental obstructive jaundice (OJ) stimulated by lipopolysaccharide (LPS) in this study. We randomized 40 rats into five groups. Group A: Sham (n = 8); group B: OJ (n = 8); group C: OJ + lipopolysaccharide (LPS; n = 8); group D: OJ + NAC + LPS (n = 8); group E: OJ + LPS + NAC (n = 8). OJ was performed by common bile duct ligation and division in all groups except the sham group. At the fifth day, the rats were jaundiced. At the fifth day of OJ, LPS was injected 10 mg/kg intraperitoneally to the rats and at the tenth day, the rats were sacrificed in group C. In group D; at the fifth day of OJ, NAC was started 100 mg/kg subcutaneously and the same dose NAC injection repeated every day for 5 days. At the tenth day of OJ, LPS was injected 10 mg/kg intraperitoneally to the rats and then after 6 h they were sacrificed. In group E; 10 mg/kg LPS was administered intraperitoneally at fifth day of OJ and after then NAC was started 100 mg/kg subcutaneously and the same dose NAC injection repeated every day for 5 days and at the tenth day, the rats were sacrificed. Tissue samples were harvested through a midline incision, and lungs were resected and examined histopathologically and immunohistochemically for tissue damage scoring. The blood was taken by cardiac puncture and malondialdehyde (MDA), myeloperoxidase (MPO), and levels of total antioxidant status were detected with biochemical methods to evaluate lung tissue damage. Increase in lung and serum MDA and MPO levels, as well as decrease in total antioxidant status, were observed in groups B and C when compared with the sham group (P = 0.0001, for each comparison). Furthermore, the lung tissue damage was observed in the same groups by histopathological examination when compared with sham group. There was significant decrease at serum and lung MPO and MDA levels after the NAC application in groups D and E, when compared with group C (P = 0.0001, for each comparison). Antioxidant status in groups D and E were increased in the presence of NAC (P = 0.0001, for each comparison). Lung histology was prevented relatively in group D when compared with groups B and C. Results of the study indicate that NAC has protective effect on pulmonary lipid peroxidation and tissue damage before and after LPS administration.