Moderate exercise training decreases inflammation in transgenic sickle cell mice

Charrin, Emmanuelle; Dubé, John J.; Connes, Philippe; Pialoux, Vincent; Ghosh, Samit; Faes, Camille; Ofori-Acquah, Solomon F.; Martin, Cyril

doi:10.1016/j.bcmd.2017.06.002

Cited by 18 publications

(19 citation statements)

References 69 publications

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“…In a recent study conducted in SCD mice, Charrin et al. () observed that endurance training increased the fraction of venous oxygen‐saturated Hb at rest and proposed that such an improvement could prevent HbS polymerization and RBC sickling, Charrin et al. () also discussed the potential beneficial effects associated with a reduction in blood acidosis related to acute exercise.…”

Section: Handling Of Blood Acidosis and Reduction Of Risk Of Vaso‐occmentioning

confidence: 99%

“…() observed that endurance training increased the fraction of venous oxygen‐saturated Hb at rest and proposed that such an improvement could prevent HbS polymerization and RBC sickling, Charrin et al. () also discussed the potential beneficial effects associated with a reduction in blood acidosis related to acute exercise. So far, no study has investigated the impacts of endurance training on blood pH in the context of SCD, although regular physical activity is commonly acknowledged to reduce blood acidosis in various conditions, such as chronic obstructive pulmonary disease (Casaburi, ).…”

Section: Handling Of Blood Acidosis and Reduction Of Risk Of Vaso‐occmentioning

confidence: 99%

“…It was suggested that an improvement in oxygen‐related mechanisms induced by regular physical activity would lower the contribution of glycolysis and thereby intramuscular acidosis (Chatel et al., ). It was concluded in that study that endurance training would be of great interest given the potential involvement of the muscle abnormalities in the pathophysiology of the disease, as documented by the reduction in the weight of the spleen in trained SCD mice (Charrin et al., , Chatel et al, ). Further studies are warranted in order to confirm the potential effects of regular physical activity on the regulation of blood acid–base balance in SCD, which could be linked to a significant improvement in the pathophysiology of the disease during and after exercise but also during activities of daily living.…”

Section: Handling Of Blood Acidosis and Reduction Of Risk Of Vaso‐occmentioning

confidence: 99%

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Do we have to consider acidosis induced by exercise as deleterious in sickle cell disease?

Chatel

Messonnier

Bendahan

2018

Experimental Physiology

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Sickle cell disease (SCD) is an inherited haemoglobin (Hb) disorder and the most common monogenic disease in the world. The root cause of this pathology is the synthesis of an abnormal Hb (HbS) that polymerizes in deoxygenated conditions, leading to the sickling of red blood cells. Acidosis is well recognized as a promoter of HbS polymerization and therefore red blood cell sickling. Indeed, it has been shown in vitro that the relative amount of sickled red blood cells increases markedly from 1% at pH 7.4 to >90% at pH 7.0. Nevertheless, no study has directly tested whether exercise-induced acidosis could favour SCD complications. Greater knowledge of the effects of metabolic acidosis during exercise could be of importance given the conclusions reached in several studies that proposed regular physical exercise as a therapeutic strategy in the management of SCD. In this review, we discuss the potential consequences of exercise-induced acidosis for the pathophysiology of SCD. We also propose some potential therapeutic interventions with the aim of reducing the metabolic acidosis related to exercise.

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Section: Handling Of Blood Acidosis and Reduction Of Risk Of Vaso‐occmentioning

confidence: 99%

Section: Handling Of Blood Acidosis and Reduction Of Risk Of Vaso‐occmentioning

confidence: 99%

Section: Handling Of Blood Acidosis and Reduction Of Risk Of Vaso‐occmentioning

confidence: 99%

See 1 more Smart Citation

Do we have to consider acidosis induced by exercise as deleterious in sickle cell disease?

Chatel

Messonnier

Bendahan

2018

Experimental Physiology

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“…As demonstrated in peripheral artery disease, a pathological condition characterized by a restriction in blood supply to peripheral tissues (McDermott, ; Pilz et al., ), endurance training could potentially be an interesting approach in the context of repeated I/R insults affecting SCD patients. In this context, regular physical activity has been associated with several beneficial effects in SCD mice, especially regarding energetics in exercising muscle (particularly, reducing acidosis; Chatel et al., ), inflammation (Charrin et al., ), haemorheological characteristics (Aufradet et al., ; Faes, Charrin, Connes, Pialoux, & Martin, ) and oxidative stress (Charrin et al., ; Chatel et al., ). These beneficial effects have been confirmed by the lower spleen weight and congestion reported in SCD mice submitted to training in comparison to their sedentary counterparts (Charrin et al., ; Chatel et al., ) and in a very recent study conducted in patients in whom moderate‐intensity endurance‐exercise training seemed to be safe and improved the functional capacity of adults with SCD (Gellen et al., ).…”

Section: Introductionmentioning

confidence: 99%

“…In this context, regular physical activity has been associated with several beneficial effects in SCD mice, especially regarding energetics in exercising muscle (particularly, reducing acidosis; Chatel et al., ), inflammation (Charrin et al., ), haemorheological characteristics (Aufradet et al., ; Faes, Charrin, Connes, Pialoux, & Martin, ) and oxidative stress (Charrin et al., ; Chatel et al., ). These beneficial effects have been confirmed by the lower spleen weight and congestion reported in SCD mice submitted to training in comparison to their sedentary counterparts (Charrin et al., ; Chatel et al., ) and in a very recent study conducted in patients in whom moderate‐intensity endurance‐exercise training seemed to be safe and improved the functional capacity of adults with SCD (Gellen et al., ). Given that oxidative stress (Charles et al., ; Lejay et al., ) and acidosis (Jubrias, Crowther, Shankland, Gronka, & Conley, ) largely impact mitochondrial respiration, it might be hypothesized that endurance training could also reduce the I/R‐induced mitochondrial dysfunction we previously reported in SCD mice (Chatel et al., ).…”

Section: Introductionmentioning

confidence: 99%

Ischaemia‐induced muscle metabolic abnormalities are poorly alleviated by endurance training in a mouse model of sickle cell disease

Chatel

Messonnier

Vilmen

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?The aim of this study was to evaluate the potential beneficial effects of endurance training during an ischaemia–reperfusion protocol in a mouse model of sickle cell disease (SCD). What is the main finding and its importance?Endurance training did not reverse the metabolic defects induced by a simulated vaso‐occlusive crisis in SCD mice, with regard to intramuscular acidosis, mitochondrial dysfunction or anatomical properties. Our results suggest that endurance training would reduce the number of vaso‐occlusive crises rather than the complications related to vaso‐occlusive crises. Abstract The aim of this study was to investigate whether endurance training could limit the abnormalities described in a mouse model of sickle cell disease (SCD) in response to an ischaemia–reperfusion (I/R) protocol. Ten sedentary (HbSS‐SED) and nine endurance‐trained (HbSS‐END) SCD mice were submitted to a standardized protocol of I/R of the leg, during which ATP, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured using magnetic resonance spectroscopy. Forty‐eight hours later, skeletal muscles were harvested. Oxidative stress markers were then measured. Although the time course of protons accumulation was slightly different between trained and sedentary mice (P < 0.05), the extent of acidosis was similar at the end of the ischaemic period. The initial rate of phosphocreatine resynthesis measured at blood flow restoration, illustrating mitochondrial function, was not altered in trained mice compared with sedentary mice. Although several oxidative stress markers were not different between groups (P > 0.05), the I/R‐related increase of uric acid concentration observed in sedentary SCD mice (P < 0.05) was not present in the trained group. The spleen weight, generally used as a marker of the severity of the disease, was not different between groups (P > 0.05). In conclusion, endurance training did not limit the metabolic consequences of an I/R protocol in skeletal muscle of SCD mice, suggesting that the reduction in the severity of the disease previously demonstrated in the basal state would be attributable to a reduction of the occurrence of vaso‐occlusive crises rather than a decrease of the deleterious effects of vaso‐occlusive crises.

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Exercise and training in sickle cell disease: Safety, potential benefits, and recommendations

Connes,

Stauffer,

Liem

et al. 2024

American J Hematol

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Sickle cell disease (SCD) is a genetic disorder characterized by complex pathophysiological mechanisms leading to vaso‐occlusive crisis, chronic pain, chronic hemolytic anemia, and vascular complications, which require considerations for exercise and physical activity. This review aims to elucidate the safety, potential benefits, and recommendations regarding exercise and training in individuals with SCD. SCD patients are characterized by decreased exercise capacity and tolerance. Acute intense exercise may be accompanied by biological changes (acidosis, increased oxidative stress, and dehydration) that could increase the risk of red blood cell sickling and acute clinical complications. However, recent findings suggest that controlled exercise training is safe and well tolerated by SCD patients and could confer benefits in disease management. Regular endurance exercises of submaximal intensity or exercise interventions incorporating resistance training have been shown to improve cardiorespiratory and muscle function in SCD, which may improve quality of life. Recommendations for exercise prescription in SCD should be based on accurate clinical and functional evaluations, taking into account disease phenotype and cardiorespiratory status at rest and in response to exercise. Exercise programs should include gradual progression, incorporating adequate warm‐up, cool‐down, and hydration strategies. Exercise training represents promising therapeutic strategy in the management of SCD. It is now time to move through the investigation of long‐term biological, physiological, and clinical effects of regular physical activity in SCD patients.

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Moderate exercise training decreases inflammation in transgenic sickle cell mice

Cited by 18 publications

References 69 publications

Do we have to consider acidosis induced by exercise as deleterious in sickle cell disease?

Do we have to consider acidosis induced by exercise as deleterious in sickle cell disease?

Ischaemia‐induced muscle metabolic abnormalities are poorly alleviated by endurance training in a mouse model of sickle cell disease

Exercise and training in sickle cell disease: Safety, potential benefits, and recommendations

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