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Systemic Oxidative Stress (systemic + oxidative_stress)
Selected AbstractsGlutathione depletion and cardiomyocyte apoptosis in viral myocarditisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2004V. Kytö Abstract Background, The course of viral myocarditis is highly variable. Oxidative stress and Bcl-2 family genes may play a role in its pathogenesis by regulating the amount of cardiomyocyte apoptosis. Apoptosis is difficult to detect and quantify in vivo. Therefore, we set to look for indicators of this potentially preventable form of cell death during various phases of experimental murine coxsackievirus B3 myocarditis. Methods, BALB/c mice were infected with the cardiotropic coxsackievirus B3 variant. Glutathione (HPLC), cardiomyocyte apoptosis (TUNEL and caspase-3 cleavage), Bax and Bcl-XL mRNA expression (real time RT-PCR), histopathology and viral replication (plaque assay and real time RT-PCR) were measured from day 3 to day 20 after infection. Results, Infection caused severe myocarditis and led to progressive decrease of plasma glutathione levels. Myocardial mRNA levels of pro-apoptotic Bax and antiapoptotic Bcl-XL were significantly increased from day 3 onwards. Bax mRNA and ratio of Bax to Bcl-XL correlated with cardiomyocyte apoptosis (r = 0·77, P = < 0·001 and r 0·51, P < 0·01, respectively). Cardiomyocyte apoptosis was highest on day 5, coinciding with a rapid decline in plasma glutathione (r = ,0·52, P = 0·003). Conclusions, Systemic oxidative stress as indicated by decreased plasma glutathione levels coincides with cardiomyocyte apoptosis in experimental coxsackievirus myocarditis. Decreased plasma glutathione levels and changes in cardiac Bax and Bcl-XL mRNA expression identify a phase of myocarditis in which the potentially preventable cardiomyocyte apoptosis is mostly observed. [source] INCREASED SYSTEMIC OXIDATIVE AND NITRATIVE STRESS IN A NEW CONGENIC MODEL OF METABOLIC SYNDROME DERIVED FROM STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND ZUCKER FATTY RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2007Yu Yamaguchi SUMMARY 1Oxidative stress has been recognized as an important factor in the biology of lifestyle-related diseases. Systemic oxidative stress may increase in metabolic syndrome characterized by a cluster of metabolic risk factors. To confirm this hypothesis, we investigated systemic oxidative/nitrative stress in a new congenic model of metabolic syndrome, namely SHRSP/ZF rats, which are derived from stroke-prone spontaneously hypertensive (SHRSP) and Zucker fatty (Zucker) rats. 2The SHRSP/ZF rats display obesity, hypertension, hyperlipidaemia, hyperglycaemia and glucose intolerance. At 6 weeks of age, SHRSP/ZF rats already showed increases in serum levels of thiobarbituric acid-reactive substances (TBARS) and oxidatively modified low-density lipoprotein (Ox-LDL) compared with lean SHRSP littermates and Zucker rats, whereas serum levels of 8-hydroxy-2,-deoxyguanine (8-OHdG), 3-nitrotyrosine, 3-chlorotyrosine and high-sensitivity C-reactive protein (hsCRP), an inflammatory marker, did not differ significantly among the three rat strains. However, levels of these oxidative/nirative stress markers in SHRSP/ZF rats, as well as in SHRSP, increased gradually with age. After 36 weeks of age, the levels of TBARS, 8-OHdG, 3-nitrotyrosine and hsCRP in SHRSP/ZF rats increased rapidly and three of six rats died thereafter. Increased oxidative/nitrative stress may be associated with death in these rats. 3Our findings indicate that systemic oxidative/nitrative stress is evidently increased in metabolic syndrome. [source] Evaluation of systemic oxidative status and mononuclear leukocytes DNA damage in children with caustic esophageal strictureDISEASES OF THE ESOPHAGUS, Issue 4 2006M. Kaya SUMMARY., Esophageal stricture (ES) due to accidentally caustic digestions is a common problem in children. Mucosal damage and repeated dilatations lead to chronic inflammation and finally ES. We investigated the oxidative status and DNA damage of children with ES. Five children with ES were compared with the same age- and sex-matched healthy subjects. Oxidative status of plasma was evaluated by measuring myeloperoxidase (MPO) activity, and total peroxide (TP) level. Anti-oxidative status of the plasma was evaluated by measuring catalase (CAT) activity, and total antioxidant response (TAR). We used the Single Cell Gel Electrophoresis (also called Comet Assay) to measure DNA strand break in peripheral blood mononuclear leukocytes. Mean MPO activity and TP levels in the ES group were significantly higher than the control group (0.83 ± 0.35, 0.09 ± 0.03 and 0.98 ± 0.38, 0.34 ± 0.20, P = 0.009 and P = 0.047 respectively). There was no significant difference in CAT activity and TAR levels between the two groups (P = 0.347). DNA damage in patients with ES was increased compared to control subjects (108.8 ± 51.2 and 57.6 ± 31.2 arbitrary units, respectively), but this difference was not significant statistically (P= 0.09). This study shows that systemic oxidative stress and alteration at the nuclear level occur in patients with ES, as a result of multiple dilatations and tissue injury. On the other hand, these results support that patients with ES may benefit from antioxidant treatment. [source] Effects of ageing on carbonyl stress and antioxidant defense in RBCs of obese Type 2 diabetic patientsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2005Alina Constantin Abstract In this study we investigated the effects of ageing on the carbonyl stress (protein carbonyls and 4-hydroxy-2-nonenal groups) and glutathione antioxidant defense in red blood cells (RBCs) of obese Type 2 diabetic patients with/without hypertensive complications. To this purpose the following methods were used: spectrophotometry (protein carbonyls, glutathione and glutathione peroxidase assays), immunofluorescence (4-hydroxy-2-nonenal localization), western blotting (immunodetection of carbonylated proteins). The results showed that compared to RBCs of healthy subjects, in obese Type 2 diabetics, ageing is associated with: (i) an increase in the concentration and expression of carbonylated proteins, a marker of oxidative stress; (ii) a decrease of both non-enzymatic and enzymatic endogenous glutathione defenses; (iii) a severely disturbed oxidant/antioxidant balance when obesity was associated with hypertension. The simultaneous insults of high blood pressure, obesity, and diabetes conducted to the highest carbonyl strss, exposure of 4-hydroxy-2-nonenal Michel adducts at the outer leaflet of RBCs plasmalemma, and the lowest glutathione antioxidant potential, particularly in elderly patients. These results can explain the gradual age-dependent diminishment of the detoxification potenital of RBCs that at the old age can not overcome the deleterious effects of the high systemic oxidative stress. [source] Mass spectrometric characterization of covalent modification of human serum albumin by 4-hydroxy- trans -2-nonenalJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 9 2006Giancarlo Aldini Abstract Several pieces of evidence indicate that albumin modified by HNE is a promising biomarker of systemic oxidative stress and that HNE-modified albumin may contribute to the immune reactions triggered by lipid peroxidation-derived antigens. In this study, we found by HPLC analysis that HNE is rapidly quenched by human serum albumin (HSA) because of the covalent adduction to the different accessible nucleophilic residues of the protein, as demonstrated by electrospray ionization mass spectrometry (ESI-MS) direct infusion experiments (one to nine HNE adducts, depending on the molar ratio used, from 1 : 0.25 to 1 : 5 HSA : HNE). An LC-ESI-MS/MS approach was then applied to enzymatically digested HNE-modified albumin, which permitted the identification of 11 different HNE adducts, 8 Michael adducts (MA) and 3 Schiff bases (SB), involving nine nucleophilic sites, namely: His67 (MA), His146 (MA), His242 (MA), His288 (MA), His510 (MA), Lys 195 (SB), Lys 199 (MA, SB), Lys525 (MA, SB) and Cys34 (MA). The most reactive HNE-adduction site was found to be Cys34 (MA) followed by Lys199, which primarily reacts through the formation of a Schiff base, and His146, giving the corresponding HNE Michael adduct. These albumin modifications are suitable tags of HNE-adducted albumin and could be useful biomarkers of oxidative and carbonylation damage in humans. Copyright © 2006 John Wiley & Sons, Ltd. [source] High preoperative recipient plasma 7,-hydroxycholesterol is associated with initial poor graft function after liver transplantationLIVER TRANSPLANTATION, Issue 12 2005Stefano Ginanni Corradini Oxidative stress is implicated in the pathogenesis of hepatic ischemia-reperfusion injury, a major determinant of initial poor graft function (IPGF) after orthotopic liver transplantation (OLT). We prospectively investigated the association between the recipient plasma preoperative oxidative stress and the occurrence of IPGF after deceased-donor OLT and indirectly studied the source,hepatic or extra-hepatic,of systemic oxidative stress in vivo in cirrhosis. We used a recently developed specific and sensitive mass spectrometry assay to measure 7,-hydroxycholesterol and 7-ketocholesterol (oxysterols), markers of oxidative stress, in biological matrices. At univariate analysis, preoperative recipient 7,-hydroxycholesterol plasma concentration was significantly higher in transplants with subsequent IPGF (n = 9) compared with those with initial good graft function (IGGF; n = 23) [mean ± SD: 30.63 ± 26.42 and 11.57 ± 15.76 ng/mL, respectively] (P = 0.017). In a logistic regression model, which included also the Model for End-Stage Liver Disease (MELD) score, 7,-hydroxycholesterol plasma concentration was an independent predictor of IPGF with an odds ratio of 1.17 (95% CI, 1.02-1.33, P = 0.028). Patients with cirrhosis (n = 32) had increased oxysterol plasma levels compared with healthy controls (n = 49); livers with cirrhosis (n = 21), however, had oxysterol content comparable with normal livers obtained from organ donors (n = 19). Oxysterols persisted elevated in plasma 1 month after OLT (n = 23). In conclusion, cirrhosis presents upregulated systemic oxidative stress likely of extrahepatic source that is associated with graft failure after OLT. (Liver Transpl 2005.) [source] Alterations of Mitochondria in Peripheral Blood Mononuclear Cells of Vitiligo PatientsPIGMENT CELL & MELANOMA RESEARCH, Issue 5 2003Maria Lucia Dell'Anna The possible role for a defective mitochondrial functionality in the pathogenesis of vitiligo was investigated by measuring intracellular levels of reactive oxygen species and of antioxidants, the activity of Krebs cycle enzymes, as well as the effects of inhibitors of the electron transport chain, in peripheral blood mononuclear cells from patients with active or stable disease vs. normal subjects. Plasma glyoxal levels were also determined in the same groups of subjects as an index of systemic oxidative stress. In patients with vitiligo in active phase, we observed an increased intracellular production of reactive oxygen species with a consequent imbalance of the prooxidant/antioxidant equilibrium, whereas plasma did not show apparent alterations in glyoxal levels, ruling out a systemic oxidative stress. In patients with stable disease, the balance between pro-oxidants and anti-oxidants seems to be maintained. Moreover, a marked increase in the expression of mitochondrial malate dehydrogenase activity and a specific sensitivity to electron transport chain complex I inhibitor were observed. Overall, these data provide further evidence for an altered mitochondrial functionality in vitiligo patients. [source] INCREASED SYSTEMIC OXIDATIVE AND NITRATIVE STRESS IN A NEW CONGENIC MODEL OF METABOLIC SYNDROME DERIVED FROM STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND ZUCKER FATTY RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2007Yu Yamaguchi SUMMARY 1Oxidative stress has been recognized as an important factor in the biology of lifestyle-related diseases. Systemic oxidative stress may increase in metabolic syndrome characterized by a cluster of metabolic risk factors. To confirm this hypothesis, we investigated systemic oxidative/nitrative stress in a new congenic model of metabolic syndrome, namely SHRSP/ZF rats, which are derived from stroke-prone spontaneously hypertensive (SHRSP) and Zucker fatty (Zucker) rats. 2The SHRSP/ZF rats display obesity, hypertension, hyperlipidaemia, hyperglycaemia and glucose intolerance. At 6 weeks of age, SHRSP/ZF rats already showed increases in serum levels of thiobarbituric acid-reactive substances (TBARS) and oxidatively modified low-density lipoprotein (Ox-LDL) compared with lean SHRSP littermates and Zucker rats, whereas serum levels of 8-hydroxy-2,-deoxyguanine (8-OHdG), 3-nitrotyrosine, 3-chlorotyrosine and high-sensitivity C-reactive protein (hsCRP), an inflammatory marker, did not differ significantly among the three rat strains. However, levels of these oxidative/nirative stress markers in SHRSP/ZF rats, as well as in SHRSP, increased gradually with age. After 36 weeks of age, the levels of TBARS, 8-OHdG, 3-nitrotyrosine and hsCRP in SHRSP/ZF rats increased rapidly and three of six rats died thereafter. Increased oxidative/nitrative stress may be associated with death in these rats. 3Our findings indicate that systemic oxidative/nitrative stress is evidently increased in metabolic syndrome. [source] |