Izabela Berdowska

Advanced oxidation protein products (AOPPs) in juvenile overweight and obesity prior to and following weight reduction

OBJECTIVES To evaluate the formation of advanced oxidation protein products (AOPPs) in juvenile overweight/obesity and obesity-related disorders and to investigate the effect of weight reduction on AOPPs. DESIGN AND METHODS AOPPs were determined in 114 overweight/obese children and adolescents without/with insulin resistance and metabolic syndrome and compared with 53 lean controls. Measurements were repeated following weight reduction program (diet/exercise, bran-enriched diet/exercise, and diet/exercise plus metformin). RESULTS Overweight/obese subjects had higher AOPPs than lean controls, more elevated in patients with co-occurring metabolic syndrome. AOPPs positively correlated with central obesity, triglycerides, lipid peroxidation and insulin, and negatively with glucose to insulin ratio. AOPPs decreased following obesity intervention and DeltaAOPPs correlated with DeltaBMI%. AOPPs reduction was more pronounced in subjects on bran-enriched diet. Baseline AOPPs were a better predictor of clinically significant weight reduction than BMI%. CONCLUSIONS Juvenile overweight/obesity was associated with AOPPs accumulation, more pronounced in metabolic syndrome. Body mass reduction decreased oxidative stress, with bran-enriched diet being more effective than diet/exercise alone.

Enhanced formation of advanced oxidation protein products in IBD

Background: Advanced oxidation protein products (AOPPs) are new protein markers of oxidative stress with pro‐inflammatory properties, accumulated in many pathological conditions. The issue of their enhanced formation in IBD has not been addressed yet. Methods: The concentration of relative AOPPs (rAOPP; concentration of AOPPs divided by albumin level) were measured in 68 subjects with ulcerative colitis (UC), 50 subjects with Crohns disease (CD) and 45 healthy volunteers, and related to disease phenotype, clinical and biochemical activity, and therapeutic strategy. Diagnostic utility of rAOPP was evaluated by ROC analysis. Results: In comparison with controls (1.367 &mgr;mol/g), rAOPP were increased in inactive (1.778 &mgr;mol/g, P = 0.053) and active (1.895 &mgr;mol/g, P = 0.013) UC and in active (1.847 &mgr;mol/g, P = 0.003) CD. In CD, but not UC, rAOPP correlated with disease activity (r = 0.42, P = 0.013). Significant correlations with the inflammatory/malnutrition indices‐erythrocyte sedimentation rate (ESR) (r = 0.53), leukocytes (r = 0.33), platelets (r = 0.38), IL‐6 (r = 0.36), and transferrin (r = −0.35) were demonstrated in CD. In UC, rAOPP correlated only with ESR (r = 0.35) and IL‐6 (r = 0.30). Instead, associations with antioxidant dismutase (r = 0.29) and catalase (r = 0.22) were observed. The diagnostic power of rAOPP in discriminating diseased from non‐diseased subjects was less than that of C‐reactive protein (CRP). Simultaneous determination of rAOPP and CRP did not significantly improve the power of single CRP determination. Conclusions: IBD was associated with enhanced formation of AOPP, which differed between C and UC with respect to the relationship between rAOPP and disease activity, inflammatory and antioxidant response. These differences may reflect divergent ways that oxidative stress develops in CD and UC. The diagnostic power of rAOPP was insufficient for its clinical application.

Paraoxonase-1 status in Crohn's disease and ulcerative colitis

Background: Paraoxonase 1 (PON1) is an extracellular enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, immunomodulator, and/or quorum‐quenching factor. There are no data on PON1 activity in Crohns disease (CD). Methods: PON1 phenotype and activity were determined spectrophotometrically in 52 subjects with CD, 67 with ulcerative colitis (UC), and 99 healthy individuals, and related to lipid peroxidation and disease phenotype, clinical and biochemical activity, and therapeutic strategy. Diagnostic utility of PON1 was evaluated by ROC analysis and compared with C‐reactive protein (CRP). Results: In comparison with controls (166 U), PON1 was reduced only in active CD (110 U, P < 0.0001) and UC (126 U, P < 0.0001), and correlated with disease activity (r = −0.47, P = 0.001 in CD and r = −0.50, P < 0.001 in UC). PON1 significantly correlated with erythrocyte sedimentation rate (ESR) (r = −0.36), platelets (r = −0.35), interleukin‐6 (r = −0.45), hemoglobin (r = 0.29), transferrin (r = 0.46), albumin (r = 0.60) in CD, and CRP (r = −0.29), ESR (r = −0.37), platelets (r = −0.43), leukocytes (r = −0.50), interleukin‐6 (r = −0.45), hemoglobin (r = 0.34), transferrin (r = 0.54), and albumin (r = 0.50) in UC. PON1 correlated positively with lipids but not with their peroxidation markers (thiobarbituric acid‐reactive substances, lipid hydroperoxides, ox‐LDL, and ox‐LDL autoantibodies). PON1 phenotype B (protective against IBD) tended to be less frequent in IBD patients than controls, and associated with lower concentration of inflammatory indices. PON1 was a poorer indicator of CD or UC than CRP. Conclusions: PON1 was reduced in IBD, despite treatment with antioxidant 5′‐aminosalicylate derivatives. PON1 reflected disease activity, inflammation severity, and anemia but not lipid peroxidation. The diagnostic power of PON1 was insufficient for its clinical application.

Impaired Erythrocyte Antioxidant Defense in Active Inflammatory Bowel Disease: Impact of Anemia and Treatment

Background: Oxidative stress contributes to the propagation and exacerbation of inflammatory bowel disease (IBD) but the status of erythrocyte antioxidant defense remains unknown. Methods: Erythrocyte activities of superoxide dismutase‐1 (SOD1), catalase, and glutathione peroxidase‐1 (GPx1) were determined in 174 IBD patients and 105 controls and referred to IBD activity, inflammation severity, nutritional status, systemic oxidative stress, anemia, and treatment. Results: Catalase and GPx1 activities were decreased in active IBD, whereas SOD1 became upregulated by IBD‐related oxidative stress. In Crohns disease (CD) corticosteroids decreased SOD1 activity. SOD1 correlated indirectly with CD activity and erythrocyte sedimentation rate (ESR) and directly with transferrin. In ulcerative colitis (UC) anemia downregulated SOD1. Decreases in GPx activity corresponded with IBD activity, anemia, inflammation, and malnutrition. Oxidative stress in UC and corticosteroids in CD also downregulated GPx. Catalase activity was decreased by CD‐related anemia, correlating directly with hemoglobin, and indirectly with CD activity, inflammatory and protein oxidative stress markers. When co‐analyzed, anemia but not CD activity significantly contributed to catalase downregulation. In UC, catalase activity corresponded indirectly with UC endoscopic activity and inflammation and directly with hemoglobin. UC activity, anemia, and treatment with azathioprine negatively affected catalase. As indicators of active IBD, GPx1 showed a diagnostic accuracy of 73%, whereas catalase showed 63% as compared to 74% of C‐reactive protein and ESR. Conclusions: Erythrocyte antioxidant defense is impaired in active IBD. SOD1, GPx1, and CAT activities are differently affected by the disease type, activity, anemia, inflammation, oxidative stress, and treatment. As an active IBD indicator, GPx1 was comparable to C‐reactive protein and ESR. Inflamm Bowel Dis 2010

Fluorescence studies on glyceraldehyde-3-phosphate dehydrogenase from bovine heart muscle.

Abstract Glyceraldehyde-3-phosphate Dehydrogenase, ATP, Flu orescence Glyceraldehyde-3-phosphate dehydrogenase is a glycolytic enzyme that catalyses conversion of glyceralde-hyde-3-phosphate to 1,3-diphosphoglycerate. ATP has been found to have an inhibitory effect on this enzyme. To establish the interaction between the enzyme and ATP, a fluorescence technique was used. Fluorescence quenching in the presence of ATP suggests cooperative binding of ATP to the enzyme (the Hill obtained coefficient equals 2.78). The interaction between glyceralde-hyde-3-phosphate dehydrogenase and ATP may control not only glycolysis but other activities of this enzyme, such as binding to the cytoskeleton.