Chronic Physical Activity In Transgenic Sad Mice

Abstract

Sickle cell anaemia (SCA) is characterized by hemorheological disorders, enhanced oxidative stress and impaired vascular function which promote the risk to trigger acute painful vaso-occlusive crises (VOC). The finding of new therapeutic approaches to improve the biological profile and the clinical management of SCA patients is a permanent challenge. As for cardiac and metabolic diseases, individualized chronic exercise programs have been suggested to improve the health status in SCA but until now no study tested this hypothesis in humans because of the vaso-occlusive risks that SCA patients could encounter during such a protocol. PURPOSE: To determine if 8 weeks of voluntary wheel running may improve blood rheology and nitric oxide bioavailability (NOx) and reduce oxidative stress in transgenic sickle mice model. METHODS: C57Bl/6J (C57) and transgenic SAD mice (31.7 ±3.6 weeks old) were randomly divided in sedentary (SED) or physical activity (PA) group. C57PA and SADPA were housed in cages equipped with running wheels. After 8 weeks, mice were euthanized either after normoxic conditions or hypoxia/reoxygenation (H/R) stress (4 hours at 6.5% oxygen followed by 2 hours of reoxygenation in ambient air). Blood samples were used to measure hematocrit and blood viscosity at two shear rates (18.75 and 375 s-1) and hematocrit-to-blood viscosity ratio (HVR) was calculated as the ratio of both values. Oxidative stress markers (malondialdehyde, MDA) and antioxidant enzymes (glutathione peroxidase, GPX; superoxide dismutase, SOD, catalase) were assayed on the heart and NOx levels were determined in the lungs using nitrite/nitrate assay. RESULTS: Chronic exercise training decreased blood viscosity (-18.2%, P<0.05), increased HVR ratio (+40%, P<0.01) at moderate shear rate but not at high shear rate and enhanced enzymatic antioxidant activity of GPX (+96%, P<0.05) in normoxia in SAD mice. Simultaneously in response to H/R stress MDA and NOx concentrations respectively decreased (-22.4%, P<0.05) and increased (P<0.05) in SADPA mice compared with SADSED. CONCLUSION: Physical activity in SAD mice seems to be an efficient way to reduce biological factors involved in VOC events via the improvement of microvascular blood flow, redox status and NOx bioavailability.