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Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise.
Gano, LB, Donato, AJ, Pierce, GL, Pasha, HM, Magerko, KA, Roeca, C, Seals, DR
Physiological genomics. 2011;(14):895-902
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Abstract
We tested the hypothesis that peripheral blood mononuclear cells (PBMC) of older adults demonstrate a proinflammatory/-oxidative gene expression profile that can be improved by regular aerobic exercise. PBMC were isolated from young (n = 25, 18-33 yr) and middle-aged/older (n = 40, 50-76 yr) healthy adults. The older adults had greater mRNA expression (real-time RT-PCR) of the proinflammatory/-oxidant transcription factor nuclear factor-κB (1.58-fold, P < 0.05) and receptor for advanced glycation end products (1.12-fold, P < 0.05), the proinflammatory cytokines tumor necrosis factor-α (1.90-fold, P < 0.05) and monocyte chemoattractant protein-1 (1.47-fold, P < 0.05), and the oxidant-producing enzymes nicotinamide adenine dinucleotide phosphate-oxidase (0.91-fold, P < 0.05) and inducible nitric oxide synthase (2.60-fold, P < 0.05). In 11 subjects (58-70 yr), maximal oxygen consumption (+11%) and exercise time (+19%) were increased (both P < 0.001), and expression of the above proinflammatory/-oxidative genes was or tended to be decreased in PBMC after vs. before 2 mo of aerobic exercise (brisk walking ∼6 days/wk, 50 min/day, 70% of maximal heart rate). Expression of interleukin-6 was not different with age or exercise intervention. Age group- and exercise intervention-related differences in gene expression were independent of other factors. PBMC of healthy older adults demonstrate increased expression of several genes associated with inflammation and oxidative stress, which is largely ameliorated by habitual aerobic exercise. This proinflammatory/-oxidative gene signature may represent a therapeutic target for lifestyle and pharmacological prevention and treatment strategies.
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Inflammation and oxidant-stress in beta-thalassemia patients treated with iron chelators deferasirox (ICL670) or deferoxamine: an ancillary study of the Novartis CICL670A0107 trial.
Walter, PB, Macklin, EA, Porter, J, Evans, P, Kwiatkowski, JL, Neufeld, EJ, Coates, T, Giardina, PJ, Vichinsky, E, Olivieri, N, et al
Haematologica. 2008;(6):817-25
Abstract
BACKGROUND We assessed whether oxidant-stress and inflammation in beta-thalassemia could be controlled by the novel oral iron chelator deferasirox as effectively as by deferoxamine. DESIGN AND METHODS Forty-nine subjects were enrolled from seven sites and studied at baseline, and after 1, 6, and 12 months of therapy. Malondialdehyde, protein carbonyls, vitamins E and C, total non-transferrin bound iron, transferrin saturation, C-reactive protein, cytokines, serum ferritin concentration and liver iron concentration were measured. RESULTS Liver iron concentration and ferritin declined significantly in both treatment groups during the study. This paralleled a significant decline in the oxidative-stress marker malondialdehyde (deferasirox -22%/year, deferoxamine -28%/year, average decline p=0.006). The rates of decline did not differ between treatment groups. Malondialdehyde was higher in both treatment groups than in a group of 30 non-thalassemic controls (p < 0.001). The inflammatory marker high-sensitivity C-reactive protein decreased significantly only in the group receiving deferasirox (deferasirox -51%/year, deferoxamine +8.5%/year, p = 0.02). This result was confounded by a chance difference in the level of high-sensitivity C-reactive protein between the two groups at baseline, but analyses controlling for this difference suggested an equally large treatment effect. CONCLUSIONS Iron chelation therapy with deferoxamine or with deferasirox was equally effective in decreasing iron burden and malondialdehyde. The possible differential effect of the two chelators on inflammation warrants further investigation.
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Regular consumption of a flavanol-rich chocolate can improve oxidant stress in young soccer players.
Fraga, CG, Actis-Goretta, L, Ottaviani, JI, Carrasquedo, F, Lotito, SB, Lazarus, S, Schmitz, HH, Keen, CL
Clinical & developmental immunology. 2005;(1):11-7
Abstract
The consumption of a diet rich in certain flavonoids, including the flavanol sub-class, has been associated with a reduced risk for vascular disease. We evaluated the effects of the regular consumption (14 d) of a flavanol-containing milk chocolate (FCMC) or cocoa butter chocolate (CBC) on variables related to vascular disease risk, oxidative stress and physical activity. Twenty-eight free-living, young (18-20 years old) male soccer players consumed daily 105 g of FCMC (168 mg of flavanols) or CBC (< 5 mg of flavanols), as part of their normal diet. The consumption of FCMC was significantly associated with a decrease in diastolic blood pressure (- 5 mm Hg), mean blood pressure (- 5 mm Hg), plasma cholesterol (-11%), LDL-cholesterol (-15%), malondialdehyde (- 12%), urate (- 11%) and lactate dehydrogenase (LDH) activity (- 11%), and an increase in vitamin E/cholesterol (+ 12%). No relevant changes in these variables were associated with CBC consumption. No changes in the plasma levels of (-)-epicatechin were observed following analysis of fasting blood samples. In conclusion, FCMC consumption was associated with changes in several variables often associated with cardiovascular health and oxidant stress. The presence of significant quantities of flavanols in FCMC is likely to have been one of the contributing factors to these results.