Abstract

The capillary regression in skeletal muscles associated with a chronic decrease in activity is related to a dysfunction of endocapillary cells induced by over-expression of oxidative stress. We hypothesized that treatment with astaxanthin, an antioxidant, would attenuate the oxidative stress induced by decreased skeletal muscle use, and that this attenuation would prevent the associated capillary regression. The purpose of the present study was to investigate the antioxidant and preventive effects of astaxanthin on capillary regression in the soleus muscle during hindlimb unloading. Twenty-four adult male Wistar rats were assigned randomly either to a control, control plus astaxanthin treatment, hindlimb unloaded or hindlimb unloaded plus astaxanthin treatment group for 7 days. Hindlimb unloading resulted in a decrease in mean soleus absolute weight, capillary number, volume and luminal diameter. The accumulation of reactive oxygen species and the over-expression of superoxide dismutase (SOD-1), a decrease in the levels of vascular endothelial growth factor (VEGF) and its receptors, an inhibition of the angiopoietin pathway and an increase of thrombospondin-1 (TSP-1), as an anti-angiogenic factor were showed. Administration of astaxanthin attenuated the changes in SOD-1 and VEGF, up-regulated the angiogenic factors and reduced the capillary regression in the soleus of hindlimb unloaded rats. In addition, the VEGF-to-TSP1 ratio was higher in the astaxanthin treated groups than in the control and HU groups. These results suggest that astaxanthin may be an effective treatment to counter the detrimental effects of a chronic decrease in skeletal muscle use on the capillary network and associated angiogenic pathways.

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