Effects of hypoxia\u2013reoxygenation stimuli on renal redox status and nuclear factor erythroid 2-related factor 2 pathway in sickle cell SADmice

Hypoxia\u2013reoxygenation (H/R) stress is known to increase oxidative stress in transgenic sickle mice and can cause organ failure. Here we described the effects of H/R on nuclear factor erythroid 2-related factor 2 (Nrf2) as a putative regulator of redox status in the kidneys of SAD mice investigating Nrf2-regulated antioxidant enzymes. Transgenic SAD mice and healthy C57Bl/6J mice were exposed to 4 h of hypoxia followed by various times of reoxygenation at ambient air (2 or 6 h). Regardless of the conditions (i.e. normoxia or H/R), SAD mice expressed higher renal oxidative stress levels. Nuclear Nrf2 protein expression decreased after 2 h post-hypoxia only in the medulla region of the kidney and only in SAD mice. Simultaneously, haem oxygenase transcripts were affected by H/R stimulus with a significant enhancement after 2 h post-hypoxia. Similarly, hypoxia inducible factor-1 staining increased after 2 h post-hypoxia in SAD mice in both cortex and medulla areas. Our data confirm that the kidneys are organs that are particularly sensitive toH/R stimuli in sickle cell SAD mice. Also, these results suggest an effect of the duration of recovery period (short vs. long) and specific responses according to kidney areas, medulla vs. cortex, on Nrf2 expression in response to H/R stimuli in SAD mice

Hypercoagulable state in sickle cell disease

International audienc

Ventilation, Oxidative Stress, and Nitric Oxide in Hypobaric versus Normobaric Hypoxia

International audienc

Does physical activity increase or decrease the risk of sickle cell disease complications?

International audienc

Moderate exercise training decreases inflammation in transgenic sickle cell mice

International audienc

Moderate endurance exercise in patients with sickle cell anaemia: effects on oxidative stress and endothelial activation

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Cyclooxygenase-2 Inhibition Limits Angiotensin II-Induced DNA Oxidation and Protein Nitration in Humans

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Is Skeletal Muscle Dysfunction a Limiting Factor of Exercise Functional Capacity in Patients with Sickle Cell Disease?

Patients with sickle cell disease (SCD) have reduced functional capacity due to anemia and cardio–respiratory abnormalities. Recent studies also suggest the presence of muscle dysfunction. However, the interaction between exercise capacity and muscle function is currently unknown in SCD. The aim of this study was to explore how muscle dysfunction may explain the reduced functional capacity. Nineteen African healthy subjects (AA), and 24 sickle cell anemia (SS) and 18 sickle cell hemoglobin C (SC) patients were recruited. Maximal isometric torque (Tmax) was measured before and after a self-paced 6-min walk test (6-MWT). Electromyographic activity of the Vastus Lateralis was recorded. The 6-MWT distance was reduced in SS (p < 0.05) and SC (p < 0.01) patients compared to AA subjects. However, Tmax and root mean square value were not modified by the 6-MWT, showing no skeletal muscle fatigue in all groups. In a multiple linear regression model, genotype, step frequency and hematocrit were independent predictors of the 6-MWT distance in SCD patients. Our results suggest that the 6-MWT performance might be primarily explained by anemia and the self-paced step frequency in SCD patients attempting to limit metabolic cost and fatigue, which could explain the absence of muscle fatigue

Effet de l'activité physique sur l'agrégation érythrocytaire chez des patients à risque d'AVC

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Role of Gender and Physical Activity Level on Cardiovascular Risk Factors and Biomarkers of Oxidative Stress in the Elderly

Background. Cardiovascular diseases remain as the leading cause of morbidity and mortality in industrialized countries. Ageing and gender strongly modulate the risk to develop cardiovascular diseases but very few studies have investigated the impact of gender on cardiovascular diseases in the elderly, which represents a growing population. The purpose of this study was to test the impact of gender and physical activity level on several biochemical and clinical markers of cardiovascular risk in elderly individuals. Methods. Elderly individuals (318 women ( years-old) and 227 men ( years-old)) were recruited. Physical activity was measured by a questionnaire. Metabolic syndrome was defined using the National Cholesterol Education Program Expert Panel’s definition. Polysomnography and digital tonometry were used to detect obstructive sleep apnea and assess vascular reactivity, respectively. Blood was sampled to measure several oxidative stress markers and adhesion molecules. Results. The frequency of cardiovascular diseases was significantly higher in men (16.4%) than in women (6.1%) (). Body mass index ( vs. ) and glycaemia ( vs. ) were lower, and High Density Lipoprotein (HDL) ( vs. ) was higher in women compared to men (). Oxidative stress was lower in women than in men (uric acid: vs. , advanced oxidation protein products: vs. , malondialdehyde: vs. ). Physical activity was not associated with lower cardiovascular risk factors in both genders. Multivariate analyses showed an independent effect of gender on acid uric (;), advanced oxidation protein products (;), and HDL concentration (;).Conclusion. These findings suggest that biochemical cardiovascular risk factors are lower in women than men which could explain the lower cardiovascular disease proportion observed in women in the elderly.Peer Reviewe