Oxidative stress is decreased in physically active sickle cell SAD mice

Abstract

SummaryOxidative stress plays a crucial role in sickle cell disease (SCD) physiopathology. Given that chronic physical activity is known to decrease reactive oxygen species (ROS) and increase nitric oxide (NO) bioavailability in healthy subjects and in patients with cardiovascular or inflammatory pathologies, modulating these factors involved in the severity of the pathology could also be beneficial in SCD. This study aimed to determine if 8 weeks of increased physical activity (PA) by voluntary wheel running affects the hypoxia/reoxygenation (H/R) responses by reducing oxidative stress and increasing NO synthesis in sickle SAD mice. Nitrite/nitrate (NOx) concentrations, NOS3 mRNA expression and phosphorylated-endothelial nitric oxide synthase immunostaining were increased in the lungs of the PA groups after H/R stress. Moreover, lipid peroxidation in the heart was decreased in PA SAD mice. The improvement of antioxidant activity at rest and the decrease in haemolysis may explain this reduced oxidative stress. These results suggest that physical activity probably diminishes some deleterious effects of H/R stress in SAD mice and could be protective against vascular occlusions.

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

“…It was hypothesised that chronic moderate physical activity could improve NO bioavailability and thus vascular function in SCD. This is in agreement with recent work published by Charrin et al ,150 which showed that 8 weeks of voluntary exercise training decreased cardiac oxidative stress induced by H/R stress in SAD mice compared to in untrained mice. Improvement of antioxidant activity and lower haemolytic rate in the trained SAD mice may explain these adaptations.…”

“…Improvement of antioxidant activity and lower haemolytic rate in the trained SAD mice may explain these adaptations. In addition, NO production, endothelial NOS (eNOS) messenger RNA expression and eNOS activation, were increased in the lungs of trained SAD mice after the H/R stress 150. These results demonstrate that regular training in SCD could reduce oxidative stress, thereby decreasing the risks of developing chronic and acute complications in this disease.…”

Environmental determinants of severity in sickle cell disease

“…89 The clinical significance of these effects is unclear and studies in sickle mice suggested decreased oxidative stress with exercise. 90 Particular issues arise with some sports, such as swimming and skiing. Swimming can be associated with rapid skin cooling on emerging from the pool, 91 and patients are typically advised to dry themselves very rapidly, although some choose to avoid the activity, particularly if it has previously caused problems.…”

The acute phase inflammatory response to maximal exercise testing in children and young adults with sickle cell anaemia

“…Alternatively, exercise training may be associated with attenuation of the acute phase response to exercise in SCA. This is plausible given that physical training is associated with reduced endothelial activation and oxidative stress in sickle cell mice exposed to hypoxia/reoxygenation conditions (Aufradet , et al 2014, Charrin , et al 2015). With the exception of the relationship observed with absolute monocyte count, cardiopulmonary fitness was not significantly associated with the acute phase response of any other biomarker measured in this study.…”